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      Reproductive factors and hormone receptor status among very young (<35 years) breast cancer patients

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          Abstract

          The prognosis for breast cancer occurs in young women is usually poor. The impact of different reproductive factors on disease characteristics is still largely unknown. We analyzed 261 patients aged ≤35 years old who were treated at the Cancer Hospital of Fudan University, Shanghai, China. The relationships between certain reproductive factors (age at menarche, parity, number of children, breastfeeding, history of abortion, age at first full-term pregnancy and oral contraceptive (OC) use) and disease characteristics were evaluated. Compared with patients who experienced fewer full-term pregnancies (<2 times), the patients with more full-term pregnancies (≥2 times) exhibited higher percentage of ER-positive tumors (61.5%) ( P = 0.015), and patients whose age of menarche was ≥15 years exhibited a greater chance of PR-positive tumors (64.8%) ( P = 0.036) compared with those whose age of menarche was <15 years old. Additionally, patients who had taken OCs were more likely to present with late-stage tumors (II stage or later) (87.5%) ( P = 0.002) than patients who had never taken OCs. Our study provides evidence that women with more full-term pregnancies and later age at menarche are more possible to exhibit hormone receptor-positive tumors. Additionally, patients who have taken OCs are more likely to present with advanced disease.

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          Most cited references15

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          Etiology of hormone receptor-defined breast cancer: a systematic review of the literature.

          Breast cancers classified by estrogen receptor (ER) and/or progesterone receptor (PR) expression have different clinical, pathologic, and molecular features. We examined existing evidence from the epidemiologic literature as to whether breast cancers stratified by hormone receptor status are also etiologically distinct diseases. Despite limited statistical power and nonstandardized receptor assays, in aggregate, the critically evaluated studies (n = 31) suggest that the etiology of hormone receptor-defined breast cancers may be heterogeneous. Reproduction-related exposures tended to be associated with increased risk of ER-positive but not ER-negative tumors. Nulliparity and delayed childbearing were more consistently associated with increased cancer risk for ER-positive than ER-negative tumors, and early menarche was more consistently associated with ER-positive/PR-positive than ER-negative/PR-negative tumors. Postmenopausal obesity was also more consistently associated with increased risk of hormone receptor-positive than hormone receptor-negative tumors, possibly reflecting increased estrogen synthesis in adipose stores and greater bioavailability. Published data are insufficient to suggest that exogenous estrogen use (oral contraceptives or hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks associated with breast-feeding, alcohol consumption, cigarette smoking, family history of breast cancer, or premenopausal obesity did not differ by receptor status. Large population-based studies of determinants of hormone receptor-defined breast cancers defined using state-of-the-art quantitative immunostaining methods are needed to clarify the role of ER/PR expression in breast cancer etiology.
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            Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype.

            Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PgR) status. It is usually easier to decide treatment strategies in cases of double-positive/-negative phenotypes than in single-positive tumors. We have examined a large and well-characterized series of primary invasive breast carcinoma (1,944 cases) with long-term clinical follow-up and hormone therapy data. Patients were stratified according to ER and PgR expression and the study was focused on the single-positive groups (ER-/PgR+ and ER+/PgR-), to assess their main features and evaluate any prognostic and predictive difference between them and compare them with the double-positive/-negative tumors. ER+/PgR-tumors were found more frequently in elderly, postmenopausal women. The majority were grade 2 ductal/no specific type carcinomas. There was no difference between the two groups with regard to lymph node stage. Survival analyses showed no difference between the two groups in terms of disease-free interval and overall survival. However, when compared with the double-negative phenotype, ER+/PgR-showed an association with better outcome but no such survival advantage was detected in case of ER-/PgR+ tumors. In the group of patients with ER+ tumors who received adjuvant hormonal therapy, absence of PgR (ER+/PgR-) was an independent predictor of development of recurrence and shorter survival and, hence, poorer response to hormonal therapy. ER+/PgR-and ER-/PgR+ tumors are biologically and clinically distinct groups of breast cancer that may require different treatment strategies with ER-/PgR+ exhibiting more aggressive behavioral characteristics.
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              The relation between survival and age at diagnosis in breast cancer.

              We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                15 September 2015
                1 July 2015
                : 6
                : 27
                : 24571-24580
                Affiliations
                1 Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
                2 Clinical Statistics Center, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
                3 Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
                Author notes
                Correspondence to: Zhimin Shao, shaozhiming@ 123456yahoo.com
                Article
                4695207
                26304928
                1bf8c3ac-58a4-4072-b88a-7108b5a545be
                Copyright: © 2015 Jia et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 2 March 2015
                : 20 May 2015
                Categories
                Clinical Research Paper

                Oncology & Radiotherapy
                reproductive factors,menopause,parity,oral contraceptive,breast cancer
                Oncology & Radiotherapy
                reproductive factors, menopause, parity, oral contraceptive, breast cancer

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