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      Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

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      1 , , 2 , 3
      BMC Cancer
      BioMed Central

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          Abstract

          Background

          Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics.

          Methods

          In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years), we examined whether histological type (9 categories) and grade of tumor (2 combined categories) differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2) were estimated in polytomous and binary logistic regression analyses.

          Results

          Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3%) and unspecified carcinomas (5.5%). Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed <2 years after first childbirth. The proportions of medullary tumors and Paget disease were particularly high among women diagnosed 2-5 years after last birth. The high proportion of poorly differentiated tumors in women with a recent childbirth was partly explained by young age.

          Conclusion

          Our results support previous observations that reproductive factors affect the risk of histological types of breast cancer differently. Sarcomas, medullary tumors, and possible also Paget disease, may be particularly susceptible to pregnancy-related exposure.

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          Most cited references44

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          Clinical characteristics of different histologic types of breast cancer

          Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50–89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, ⩾5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER−/PR− vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30–49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.
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            Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects

            In a Norwegian, prospective study we investigated breast cancer risk in relation to age at, and time since, childbirth, and whether the timing of births modified the risk pattern after delivery. A total of 23 890 women of parity 5 or less were diagnosed with breast cancer during follow-up of 1.7 million women at ages 20–74 years. Results, based on Poisson regression analyses of person-years at risk, showed long-term protective effects of the first, as well as subsequent, pregnancies and that these were preceded by a short-term increase in risk. The magnitude and timing of this adverse effect differed somewhat by birth order, maternal age at delivery and birth spacing. No transient increase in risk was seen shortly after a first birth below age 25 years, but an early first birth did not prevent a transient increase in risk after subsequent births. In general, the magnitude of the adverse effect was strongest after pregnancies at age 30 years or older. A wide birth interval was also related to a more pronounced adverse effect. Increasing maternal age at the first and second childbirth was associated with an increase in risk in the long run, whereas no such long-term effect was seen with age at higher order births.
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              Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis.

              Little information is available on how the risk of breast cancer associated with the use of hormone therapy for menopause varies by histological type. We aimed to describe such associations for eight histological types of breast cancer. Analyses are based on 1 031 224 postmenopausal women recruited in 1996-2001 into a nationwide UK cohort study, and followed for incident cancer and death. Relative risks associated with use of hormone therapy were estimated for eight histological types of breast cancer. During 3.6 million person-years of follow-up, 14 102 breast cancers were diagnosed, of which 13 782 (98%) had histological type recorded: 11 869 (86%) were invasive, including 8007 ductal, 1526 lobular, 365 mixed ductal-lobular, 492 tubular, 71 medullary, and 148 mucinous cancers; and 1913 (14%) were in situ, including 1443 ductal and 86 lobular cancers. The relative risks of invasive breast cancer in current users compared with never users of hormone therapy varied significantly according to tumour histology overall (p<0.0001), for users of oestrogen-only therapy (p=0.0001), and for users of oestrogen-progestagen therapy (p<0.0001). The largest relative risks in current compared with never users of hormone therapy were seen for lobular (relative risk 2.25, 95% CI 2.00-2.52), mixed ductal-lobular (2.13, 1.68-2.70), and tubular cancers (2.66, 2.16-3.28). The relative risks for ductal and mucinous cancers were 1.63 (95% CI 1.55-1.72) and 1.58 (1.08-2.31), respectively. The risk of medullary cancer was not increased (0.74, 0.43-1.28). The relative risk of in-situ disease in current users compared with never users of hormone therapy also varied significantly according to histological type (p=0.03), with a relative risk for lobular carcinoma in situ of 2.82 (1.72-4.63) and 1.56 (1.38-1.75) for ductal carcinoma in situ. The effects of hormone therapy on invasive ductal, lobular, and tubular cancer were generally greater for oestrogen-progestagen therapy than for oestrogen-only therapy, and were attenuated with increasing body-mass index (BMI). The risks associated with use of hormone therapy for menopause differ by histological type of breast cancer, and are substantially attenuated with increasing BMI.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2010
                21 May 2010
                : 10
                : 226
                Affiliations
                [1 ]Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
                [2 ]Department of Mathematics, University of Bergen, Bergen, Norway
                [3 ]Gade Institute, University of Bergen, Bergen, Norway
                Article
                1471-2407-10-226
                10.1186/1471-2407-10-226
                2889893
                20492657
                65d272b3-4ab5-46b5-b16d-2199e62ceb02
                Copyright ©2010 Albrektsen et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 October 2009
                : 21 May 2010
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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