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      Breast Cancer in Young Women: Poor Survival Despite Intensive Treatment

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          Abstract

          Background

          Breast cancer is uncommon in young women and correlates with a less favourable prognosis; still it is the most frequent cancer in women under 40, accounting for 30–40% of all incident female cancer. The aim of this study was to study prognosis in young women, quantifying how much stage at diagnosis and management on the one hand, and tumour biology on the other; each contribute to the worse prognosis seen in this age group.

          Methodology/Principal Findings

          In a registry based cohort of women aged 20–69 (n = 22 017) with a primary diagnosis of invasive breast cancer (1992–2005), women aged 20–34 (n = 471), 35–39 (n = 858) and 40–49 (n = 4789) were compared with women aged 50–69 years (n = 15 899). The cumulative 5-year relative survival ratio and the relative excess mortality (RER) were calculated. The cumulative 5-year relative survival ratio was lowest in women aged 20–34. The RER was 2.84 for women aged 20–34 and decreased with increasing age (RER 1.76 and 1.17 for women aged 35–39 and 40–49, respectively). The excess risk was, however, present only in disease stages I and II. For women aged 20–34 with stage I disease RER was 4.63, and 6.70 in the subgroup with tumour size 1–10 mm. The absolute difference in stage I between the youngest and the reference groups amounted to nearly 8%, with a 90% 5-year survival in women aged 20–34. In stages IIa and IIb, the relative excess risk was not as dramatic, but the absolute differences approached 15%. The youngest women with small tumours generally received more aggressive treatment than women in older age groups.

          Conclusions

          After correction for stage, tumour characteristics and treatment, age remained an independent risk factor for breast cancer death in women <35 years of age. The excess risk for young women was only seen in early stages of disease and was most pronounced in women with small tumours. Young women affected by breast cancer have a high risk of dying compared to their middle-aged counterparts even if diagnosed early and receiving an intense treatment.

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          Most cited references34

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          The relative survival rate: a statistical methodology.

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            Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials.

            Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments. The data of two randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%). There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval [CI], 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio [HR], 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P <.01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P <.01). Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.
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              Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer.

              This analysis was performed to clarify the relationship of young age at diagnosis to the pathologic features of the tumor and prognosis in patients with early-stage breast cancer. We retrospectively analyzed data from 1,398 patients with American Joint Committee on Cancer Staging stage I or II breast cancer treated by breast-conserving therapy between 1968 and 1985. One hundred seven patients were younger than 35 years at the time of diagnosis. The median follow-up duration for the 1,032 survivors was 99 months. Patients younger than 35 years had a significantly higher overall recurrence rate (P = .002), as well as a greater risk for developing distant metastases (P = .03), when compared with older patients. The cancers in younger patients more commonly showed factors associated with a worse prognosis (including grade 3 histology, lymphatic vessel invasion [LVI], necrosis, and estrogen receptor [ER] negativity) as compared with older patients. In a proportional hazards model that included clinical and treatment-related variables, as well as these pathologic features, age younger than 35 years remained a significant predictor for time to recurrence (relative risk [RR], 1.70), time to distant failure (RR, 1.60), and overall mortality (RR, 1.50). Breast cancer patients younger than 35 years have a worse prognosis than older patients. This difference is only partially explained by a higher frequency of adverse pathologic factors seen in younger patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                11 November 2009
                : 4
                : 11
                : e7695
                Affiliations
                [1 ]Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
                [2 ]Regional Oncologic Center, Uppsala University Hospital, Uppsala, Sweden
                [3 ]Department for Surgical Science, Uppsala University Hospital, Uppsala, Sweden
                [4 ]School of Medicine, Division of Cancer Studies, King's College London, London, United Kingdom
                [5 ]Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, Uppsala, Sweden
                Health Canada, Canada
                Author notes

                Conceived and designed the experiments: HF SE JF LH IF HL. Performed the experiments: HF SE JF LH IF HL. Analyzed the data: HF SE JF LH IF HL. Contributed reagents/materials/analysis tools: HF SE JF LH IF HL. Wrote the paper: HF SE JF LH IF HL.

                Article
                09-PONE-RA-12009
                10.1371/journal.pone.0007695
                2770847
                19907646
                47f38083-23bb-409a-b6a4-a0dc1792579d
                Fredholm 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
                : 31 July 2009
                : 6 October 2009
                Page count
                Pages: 9
                Categories
                Research Article
                Oncology/Breast Cancer
                Public Health and Epidemiology/Epidemiology
                Surgery/Breast Surgery
                Women's Health/Breast Cancer
                Oncology/Breast Cancer
                Public Health and Epidemiology/Epidemiology
                Surgery/Breast Surgery
                Women's Health/Breast Cancer

                Uncategorized
                Uncategorized

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