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1.  Are two-centimeter breast cancers large or small? 
Current Oncology  2013;20(4):205-211.
Background
Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage ii, and smaller cancers, as stage i. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage i or a stage ii breast cancer.
Methods
Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1–1.9 cm, exactly 2.0 cm, and 2.1–2.9 cm.
Results
In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1–3.0 cm). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.2% for women with 21-mm to 29-mm tumours.
Conclusions
For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis.
doi:10.3747/co.20.1364
PMCID: PMC3728051  PMID: 23904761
Breast cancer; stage; survival
2.  Breast cancer in moroccan young women: a retrospective study 
BMC Research Notes  2010;3:286.
Background
Breast cancer is uncommon in young women and induces more aggressive biologic characteristics. Survival in young women has been widely studied in developed countries. Less favorable prognosis and low survival were found.
In Morocco, this study is the first investigation of clinical features, treatment and prognosis associated with breast cancer in young women.
Findings
Four hundred and nine women aged 35 years or less were included in this study. All these women were diagnosed as having breast cancer at the National Institute of Oncology in Rabat, Morocco between 2003 and 2007. The relation between clinical and therapeutic characteristics and event-free survival (EFS) and overall survival (OS) were assessed by Cox regression analysis.
The median age of the patients was 32 years. Fifty three patients (13%) have metastatic disease at diagnosis and 356 patients (87%) had localised disease. In 57.9% of the cases, the estrogen receptors status was positive. The median follow-up was 32.2 months. After 3 years the survival rate was 80.6%. In the case of localised disease, OS and EFS at 3 years were 83.2% and 62.5%, respectively. OS and EFS at 3 years was higher in patients with stage I than patients with stage II and stage III (p = 0.001). Positive estrogen receptors was significantly associated to OS and EFS at 3 years compared to negative estrogen receptors (p = 0.001). Adjuvant chemotherapy, adjuvant radiotherapy and adjuvant hormone therapy were associated with net benefit in OS and EFS at 3 years. Cox regression analysis showed that negative ER was significantly associated with poorer OS (HR = 2.42, 95% CI = 1.25 - 4.66, p < 0.009) and poorer EFS (HR = 1.73, 95%CI = 1.05 - 2.86, p = 0.03). Stage III disease were associated to poorer EFS (HR = 5.35, 95%CI = 1.60 -17.84, p = 0.006).
Conclusions
In Morocco, young women with breast cancer had less favorable prognosis. Multivariate analysis showed that negative hormone receptor status was associated with lower EFS and OS. Clinical trials should be launched to improve the survival of these young women with breast cancer.
doi:10.1186/1756-0500-3-286
PMCID: PMC2992542  PMID: 21059204
3.  Prognosis in women with interval breast cancer: population based observational cohort study 
Objective To compare the prognosis in women with interval breast cancer (cancer detected after a normal screening mammogram and before the next scheduled mammogram) with breast cancer detected among women not yet invited to mammography screening (non-screened).
Design Population based observational study.
Setting Norwegian breast cancer screening programme, implemented in different counties from 1996 to 2005.
Participants 7116 women with a diagnosis of breast cancer at age 50 to 72 years; 1816 had interval breast cancer and 5300 had a diagnosis of breast cancer but had not yet been invited to screening.
Main outcome measures Characteristics of the breast tumours, and survival of the women using Kaplan Meier curves and multivariable Cox proportional hazard models.
Results Although interval cancers on average were slightly larger than the cancers in women not invited to screening, the histological type or status of axilliary lymph nodes did not differ noticeably between the two groups. Among interval cancers, there were no appreciable trends in size, nodal status, grade, or hormone receptor positivity associated with time since the last normal mammogram as a marker of growth rate. After 10 years of follow-up, the survival rates were 79.1% (95% confidence interval 75.4% to 82.3%) among women with interval cancers and 76.8% (75.3% to 78.2%) among women in the non-screened cancer group (hazard ratio 0.98, 95% confidence interval 0.84 to 1.15; P=0.53). Analyses stratified by time since last normal mammogram, age at diagnosis, or screening round showed similar results.
Conclusion The prognosis of women with interval breast cancers was the same as that of women with breast cancers diagnosed without mammography screening.
doi:10.1136/bmj.e7536
PMCID: PMC3500095  PMID: 23160783
4.  The Effect of Pre-Diagnostic Alcohol Consumption on Survival after Breast Cancer in Young Women 
Background
Alcohol consumption has been comprehensively investigated as an etiologic risk factor for breast cancer but has received little attention in terms of its impact on prognosis after breast cancer, particularly for young women.
Methods
1286 women diagnosed with invasive breast cancer at or before 45 years of age from two population-based case-control studies in the Seattle-Puget Sound region were followed from their diagnosis of breast cancer (between January 1983 and December 1992) for survival through June 2002, during which time 364 women had died. Cox proportional hazards modeling was used to assess the effect of pre-diagnostic alcohol consumption on the risk of dying.
Results
After adjusting for age and diagnosis year, compared to non-drinkers, women who consumed alcohol in the 5 years prior to diagnosis had a decreased risk of death [>0 to <3 drinks per week: HR(hazard ratio) = 0.7 (95% CI: 0.6–0.95); 3 to <7 drinks per week: RR = 0.6 (95% CI: 0.4–0.8); ≥ 7 drinks per week: RR = 0.7 (95% CI: 0.5–0.9)]. This association was unchanged upon additional adjustment for potential confounders including most notably treatment, stage at diagnosis, and mammogram history.
Conclusion
These results suggest that women who consume alcohol prior to a diagnosis of breast cancer have improved survival which does not appear to be attributable to differences in stage, screening or treatment.
doi:10.1158/1055-9965.EPI-07-2897
PMCID: PMC2605937  PMID: 18664549
breast cancer; survival; alcohol consumption; wine; modifiable risk factor
5.  Long term prognosis of women with breast cancer in New Zealand: study of survival to 30 years. 
The long term prognosis of women with breast cancer was studied by analysing retrospectively the 30 year survival of 2019 women with histologically proved breast cancer recorded at the National Cancer Registry in New Zealand between 1950 and 1954. Excess mortality rates for successive five year survival cohorts were calculated from the survival data. From the total cohort the excess mortality rate fell rapidly during the first 10 years and then became low after 20 years. There were no significant differences in excess mortality for the age cohorts. Most of the excess mortality for 20 years was due to deaths from breast cancer. In this study the prognosis for women with breast cancer approached normal after 20 years and the improvement in prognosis resulted from decreasing death rates from breast cancer.
PMCID: PMC1548058  PMID: 6407563
6.  Adenoid Cystic Breast Carcinoma: Is Axillary Staging Necessary in All Cases? Results from the California Cancer Registry 
The breast journal  2011;17(5):485-489.
Introduction
Adenoid cystic carcinoma is an uncommon type of breast cancer. There are limited data about its epidemiology, tumor characteristics, and outcomes. Using a large, population-based database, this study aims to identify specific characteristics of patients with adenoid cystic breast cancer, investigate its natural history, and determine its long-term prognosis.
Methods
The California Cancer Registry (CCR), a population-based registry, was reviewed from the years 1988 to 2006. The data were analyzed with relation to patient age, tumor size and stage, and overall survival. Relative cumulative actuarial survival was determined using the Berkson-Gage life table method.
Results
A total of 244 cases of invasive adenoid cystic cancer were identified in women during this time period. The patients’ median age was 61.9 years. Most cases were diagnosed in non-Hispanic White women (82%, n=200), followed by African-American (6%, n=15), Asian/Pacific-Islander (5.7%, n=14) and Hispanic women (4.4%, n=12). The remainder of the patients was of unknown or other ethnicity. Tumors were between 1 and 140 mm in size. At the time of diagnosis, 92% (n=225) of patients had localized disease, 5% (n=12) of patients had regional disease, and even fewer (n=7) had either distant or unknown staged disease. Lymph node involvement was not present in any tumors smaller than 1.4 cm. The relative cumulative survival of patients with adenoid cystic breast carcinoma was 95.6% at 5 years and 94.9% at 10 years.
Conclusion
Adenoid cystic carcinoma of the breast is a rare disease with an overall good prognosis. Knowing that this cancer usually presents as localized disease, with lymph node involvement seen only with larger tumors, can help clinicians plan the operative management of these tumors.
doi:10.1111/j.1524-4741.2011.01117.x
PMCID: PMC3721506  PMID: 21790841
Adenoid Cystic Breast Carcinoma; Incidence; Prognosis; Survival; Treatment
7.  Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm 
Introduction
The difference in breast cancer incidence and prognosis between ethnic groups seeks an explanation. We have recently shown that Swedish women are two to three times more likely to be diagnosed with breast cancer compared with Singaporean women. In the present paper, we compare breast cancer survival in the two countries.
Methods
We compared the survival of 10,287 Singaporean women and 17,090 Swedish women with breast cancer. Relative survival ratios were used to describe the prognosis in the two populations. A Poisson regression model was used to calculate relative risks for different follow-up periods, age groups, time of diagnosis and disease stages.
Results
The majority of the Swedish women had local cancer (80%) compared with Singaporean women (51%). The overall 5-year relative survival of the Swedish women appeared better (80%) than that of the Singaporean women (70%). A similar survival pattern was observed, however, between the two countries in a stage-by-stage comparison. Survival improved for all women in Singapore over the two decades, but only in the premenopausal women in Stockholm. In 1980 to 1989, premenopausal Singaporean women had 27% increased risk of death compared with Swedish women, adjusted for stage and year of follow-up, while the postmenopausal women had 48% increased risk. In 1990 to 1999, this risk decreased by 19% and 22% for the premenopausal and postmenopausal Singaporean women compared with the Swedish women.
Conclusions
The stage-dependent prognosis was similar for Singaporean women and for Swedish women. Singaporean women, both premenopausal and postmenopausal, had pronounced improvement in prognosis over the calendar periods, probably contributed by marked economic improvement, leading to better medical facilities and management with increased awareness of patients to diagnosis and treatment, as well as improved treatment options. Improvement seen only in the premenopausal women in Stockholm was probably due to improved treatment options.
doi:10.1186/bcr2219
PMCID: PMC2687707  PMID: 19166618
8.  Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study 
British Journal of Cancer  2013;108(5):1195-1208.
Background:
We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries.
Methods:
We analysed the data on 257 362 women diagnosed with breast cancer during 2000–7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis.
Results:
Age-standardised 3-year net survival was 87–89% in the UK and Denmark, and 91–94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42–45% elsewhere. Women in the UK had low survival for TNM stage III–IV disease compared with other countries.
Conclusion:
International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.
doi:10.1038/bjc.2013.6
PMCID: PMC3619080  PMID: 23449362
breast cancer; survival; stage; population-based
9.  Second breast cancers in a Tuscan case series: characteristics, prognosis, and predictors of survival 
British Journal of Cancer  2008;99(3):539-544.
Little is known about long-term outcomes following a second breast cancer diagnosis. We describe the epidemiology, characteristics and prognosis of second breast cancers in an Italian cohort. We identified women with two breast cancer diagnoses from 24 278 histology records at a Tuscan breast cancer service between 1980 and 2005, and determined their survival status. Disease-specific survival from second diagnosis was examined using Cox regression analyses. Second cancers were identified in 1044 women with a median age of 60 years. In all 455 were ipsilateral relapses and 589 were contralateral cancers. Median time between first and second diagnosis was 63.4 months. The majority of second cancers was small invasive or in situ tumours. Estimated 10-year survival from a second cancer diagnosis was 78%. Survival was poorest when the second cancer was large (HR=2.26) or node-positive (HR=3.43), when the time between the two diagnoses was <5 years (HR=1.45), or when the diagnosis was in an earlier epoch (HR=2.20). Second tumours were more likely to be large or node-positive if the first breast cancer had these features. Prognosis following a second breast cancer in this cohort was generally good. However, large or node-positive second tumours, and shorter intervals between diagnoses were indicators of poorer survival.
doi:10.1038/sj.bjc.6604481
PMCID: PMC2527814  PMID: 18628762
breast cancer; contralateral cancer; disease-specific survival; ipsilateral breast relapse; prognosis
10.  The epidemiology of breast cancer in French Guiana 2003–2006 
SpringerPlus  2013;2:471.
For the first time the incidence and mortality of breast cancer were estimated in French Guiana, an overseas French Territory of South America. A certified cancer registry collected exhaustive data on breast cancer between 2003 and 2005. The age-standardized rate of breast cancer was 47.1 per 100 000 women. The age-standardized death rate was 11.0 per 100 000 women. Although the standardized incidence and death rates were lower than in metropolitan France and South America, the ratio between incidence and mortality showed that the prognosis of breast cancer in French Guiana was worse than in metropolitan France (23 deaths per 100 incident cases versus 17 deaths per 100 incident cases, respectively). The demographics of French Guiana, suggests that mass organized screening may benefit from lowering the age of its target population.
doi:10.1186/2193-1801-2-471
PMCID: PMC3786073  PMID: 24083115
Breast cancer; French Guiana Registry; Cancer incidence; Cancer in South America
11.  The influence of genetic variation in 30 selected genes on the clinical characteristics of early onset breast cancer 
Breast Cancer Research : BCR  2008;10(6):R108.
Introduction
Common variants that alter breast cancer risk are being discovered. Here, we determine how these variants influence breast cancer prognosis, risk and tumour characteristics.
Methods
We selected 1,001 women with early onset nonfamilial invasive breast cancer from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort and genotyped 206 single nucleotide polymorphisms (SNPs) across 30 candidate genes. After quality control, 899 cases and 133 SNPs remained. Survival analyses were used to identify SNPs associated with prognosis and determine their interdependency with recognized prognostic factors. To identify SNPs that alter breast cancer risk, association tests were used to compare cases with controls from the Wellcome Trust Case Control Consortium. To search for SNPs affecting tumour biology, cases were stratified into subgroups according to oestrogen receptor (ER) status and grade and tested for association.
Results
We confirmed previous associations between increased breast cancer risk and SNPs in CASP8, TOX3 (previously known as TNRC9) and ESR1. Analysis of prognosis identified eight SNPs in six genes (MAP3K1, DAPK1, LSP1, MMP7, TOX3 and ESR1) and one region without genes on 8q24 that are associated with survival. For MMP7, TOX3 and MAP3K1 the effects on survival are independent of the main recognized clinical prognostic factors. The SNP in 8q24 is more weakly associated with independent effects on survival. Once grade and pathological nodal status (pN stage) were taken into account, SNPs in ESR1 and LSP1 showed no independent survival difference, whereas the effects of the DAPK1 SNP were removed when correcting for ER status. Interestingly, effects on survival for SNPs in ESR1 were most significant when only ER-positive tumours were examined. Stratifying POSH cases by tumour characteristics identified SNPs in FGFR2 and TOX3 associated with ER-positive disease and SNPs in ATM associated with ER-negative disease.
Conclusions
We have demonstrated that several SNPs are associated with survival. In some cases this appears to be due to an effect on tumour characteristics known to have a bearing on prognosis; in other cases the effect appears to be independent of these prognostic factors. These findings require validatation by further studies in similar patient groups.
doi:10.1186/bcr2213
PMCID: PMC2656905  PMID: 19094228
12.  Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women 
PLoS ONE  2013;8(5):e63204.
Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
doi:10.1371/journal.pone.0063204
PMCID: PMC3660335  PMID: 23704896
13.  Lack of Survival Gain for Elderly Women with Breast Cancer 
The Oncologist  2011;16(4):415-423.
The relative survival of breast cancer patients diagnosed in 1995–2005 from the Netherlands Cancer Registry was examined and stratified by age group. In contrast to younger patients and in spite of similarly intensified treatment, the relative survival of elderly patients showed no improvement over this time period.
Background.
The number of elderly women with breast cancer is increasing and will become a major health concern. However, little is known about the optimal treatment for this age group. The aim of this study was to describe time trends for the overall Dutch breast cancer cohort with an emphasis on differences between young and elderly patients.
Methods.
All adult female patients diagnosed in 1995–2005 were selected from the Netherlands Cancer Registry. Relative excess risks for death (adjusted for stage, histology, treatment, and grade) were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times.
Results.
Overall, 127,805 patients were included. Treatment of patients aged ≥75 years changed significantly over time: they received less surgery, more adjuvant hormonal treatment and chemotherapy, and more hormonal treatment without surgery. In contrast to younger patients, the relative survival did not improve significantly over time for elderly patients. With increasing age, the observed–expected death ratio decreased to almost 1.0.
Conclusion.
Survival for elderly patients with breast cancer did not improve significantly. Observed–expected death ratios in the elderly are close to 1, indicating that excess mortality is low. Elderly patients with breast cancer have a higher risk for overtreatment and undertreatment, with a delicate therapeutic balance between breast cancer survival gain and potential toxicities. To improve breast cancer survival in the elderly, a critical reappraisal is needed of costs and benefits of hormonal as well as other treatments, and better selection of patients who can benefit from available therapies is warranted.
doi:10.1634/theoncologist.2010-0234
PMCID: PMC3228128  PMID: 21406470
Breast cancer; Elderly; Relative survival; Population based
14.  Lower breast cancer survival in mothers of children with a malignancy: a national study 
British Journal of Cancer  2008;98(11):1876-1878.
As it is unclear if hereditary factors affect breast cancer survival, this was compared using fertility and cancer registry data, among all women so diagnosed during 1961–1999 in Sweden, having a child with childhood cancer (⩽20 years of age; n=254) and with that of other women (n=74 781). Those having a child with a childhood malignancy had a significantly worse survival than other women, relative risk (RR)=1.25, 95% CI 1.02–1.55, P<0.04, adjusted for age at diagnosis, year of diagnosis, parity and time since last pregnancy. Childhood sarcomas or acute myeloid leukaemia seemed to be most associated with a worse survival in the mother (RR=1.38 and 1.69, respectively). The lower survival of the mother was present for breast cancer diagnosed both before and after 50 years of age. The Li–Fraumeni syndrome and possibly other genetic disorders may lower breast cancer survival.
doi:10.1038/sj.bjc.6604350
PMCID: PMC2410117  PMID: 18458676
breast cancer; childhood cancer; familial cancer; hereditary syndrome; prognosis
15.  Postdiagnosis diet quality, the combination of diet quality and recreational physical activity, and prognosis after early-stage breast cancer 
Cancer causes & control : CCC  2011;22(4):589-598.
Objective
To investigate, among women with breast cancer, how postdiagnosis diet quality and the combination of diet quality and recreational physical activity are associated with prognosis.
Methods
This multiethnic, prospective observational cohort included 670 women diagnosed with local or regional breast cancer. Thirty months after diagnosis, women completed self-report assessments on diet and physical activity and were followed for 6 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for death from any cause and breast cancer death.
Results
Women consuming better-quality diets, as defined by higher Healthy Eating Index-2005 scores, had a 60% reduced risk of death from any cause (HRQ4:Q1: 0.40, 95% CI: 0.17, 0.94) and an 88% reduced risk of death from breast cancer (HRQ4:Q1: 0.12, 95% CI: 0.02, 0.99). Compared with inactive survivors consuming poor-quality diets, survivors engaging in any recreational physical activity and consuming better-quality diets had an 89% reduced risk of death from any cause (HR: 0.11, 95% CI: 0.04, 0.36) and a 91% reduced risk of death from breast cancer (HR: 0.09, 95% CI: 0.01, 0.89). Associations observed were independent of obesity status.
Conclusion
Women diagnosed with localized or regional breast cancer may improve prognosis by adopting better-quality dietary patterns and regular recreational physical activity. Lifestyle interventions emphasizing postdiagnosis behavior changes are advisable in breast cancer survivors.
doi:10.1007/s10552-011-9732-9
PMCID: PMC3091887  PMID: 21340493
Diet; Exercise; Breast neoplasm; Prognosis
16.  Factors influencing the effect of age on prognosis in breast cancer: population based study 
BMJ : British Medical Journal  2000;320(7233):474-479.
Objective
To investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment influences such an association.
Design
Retrospective cohort study based on a population based database of patients with breast cancer containing detailed information on tumour characteristics, treatment regimens, and survival.
Setting
Denmark.
Subjects
10 356 women with primary breast cancer who were less than 50 years old at diagnosis.
Main outcome measures
Relative risk of dying within the first 10 years after diagnosis according to age at diagnosis after adjustment for known prognostic factors and expected mortality.
Results
Overall, young women with low risk disease who did not receive adjuvant treatment had a significantly increased risk of dying; risk increased with decreasing age at diagnosis (adjusted relative risk: 45-49 years (reference): 1; 40-44 years: 1.12 (95% confidence interval 0.89 to 1.40); 35-39 years: 1.40 (1.10 to 1.78); <35 years: 2.18 (1.64 to 2.89). However, no similar trend was seen in patients who received adjuvant cytotoxic treatment. The increased risk in younger women who did not receive adjuvant treatment compared with those who did remained when women were grouped according to presence of node negative disease and by tumour size.
Conclusion
The negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease who did not receive adjuvant cytotoxic treatment. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic treatment.
PMCID: PMC27289  PMID: 10678859
17.  Causes of Death and Relative Survival of Older Women After a Breast Cancer Diagnosis 
Journal of Clinical Oncology  2011;29(12):1570-1577.
Purpose
To understand the impact of breast cancer on older women's survival, we compared survival of older women diagnosed with breast cancer with matched controls.
Methods
Using the linked 1992 to 2003 Surveillance, Epidemiology, and End Results (SEER) -Medicare data set, we identified women age 67 years or older who were newly diagnosed with ductal carcinoma in situ (DCIS) or breast cancer. We identified women not diagnosed with breast cancer from the 5% random sample of Medicare beneficiaries residing in SEER areas. We matched patient cases to controls by birth year and registry (99% or 66,039 patient cases matched successfully). We assigned the start of follow-up for controls as the patient cases' date of diagnosis. Mortality data were available through 2006. We compared survival of women with breast cancer by stage with survival of controls using multivariable proportional hazards models adjusting for age at diagnosis, comorbidity, prior mammography use, and sociodemographics. We repeated these analyses stratifying by age.
Results
Median follow-up time was 7.7 years. Differences between patient cases and controls in sociodemographics and comorbidities were small (< 4%). Women diagnosed with DCIS (adjusted hazard ratio [aHR], 0.7; 95% CI, 0.7 to 0.7) or stage I disease (aHR, 0.8; 95% CI, 0.8 to 0.8) had slightly lower mortality than controls. Women diagnosed with stage II disease or higher had greater mortality than controls (stage II disease: aHR, 1.2; 95% CI, 1.2 to 1.2). The association of a breast cancer diagnosis with mortality declined with age among women with advanced disease.
Conclusion
Compared with matched controls, a diagnosis of DCIS or stage I breast cancer in older women is associated with better survival, whereas a diagnosis of stage II or higher breast cancer is associated with worse survival.
doi:10.1200/JCO.2010.33.0472
PMCID: PMC3138627  PMID: 21402602
18.  The association of waiting times from diagnosis to surgery with survival in women with localised breast cancer in England 
British Journal of Cancer  2013;109(1):42-49.
Background:
Survival from breast cancer in the United Kingdom is lower than in other developed countries. It is unclear to what extent waiting times for curative surgery affect survival.
Methods:
Using national databases for England (cancer registries, Hospital Episode Statistics and Office of National Statistics), we identified 53 689 women with localised breast cancer, aged ⩾15 years, diagnosed between 1996 and 2009, who had surgical resection with curative intent within 62 days of diagnosis. We used relative survival and excess risk modelling to determine associations between waiting times and 5-year survival.
Results:
The median diagnosis to curative surgery waiting time among breast cancer patients was 22 days (interquartile range (IQR): 15–30). Relative survival was similar among women waiting between 25 and 38 days (RS: 93.5% 95% CI: 92.8–94.2%), <25 days (RS: 93.0% 95% CI: 92.5–93.4%) and between 39 and 62 days (RS: 92.1% 95% CI: 90.8–93.4%). There was little evidence of an increase in excess mortality with longer waiting times (excess hazard ratio (EHR): 1.06; 95% CI: 0.88–1.27 comparing waiting times 39-62 with 25–38 days). Excess mortality was associated with age (EHR 65–74 vs 15–44 year olds: 1.23; 95% CI: 1.07–1.41) and deprivation (EHR most vs least deprived: 1.28; 95% CI: 1.09–1.49), but waiting times did not explain these differences.
Conclusion:
Within 62 days of diagnosis, decreasing waiting times from diagnosis to surgery had little impact on survival from localised breast cancer.
doi:10.1038/bjc.2013.317
PMCID: PMC3708566  PMID: 23799851
waiting times; cancer survival; breast cancer; surgery
19.  Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women 
Introduction
Young women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women.
Methods
Data for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010.
Results
With up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease.
Conclusions
Among AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women.
doi:10.1186/bcr3556
PMCID: PMC3978627  PMID: 24131591
20.  Age at Diagnosis and Breast Cancer Survival in Iran 
Background. Tumour characteristics are the most important prognostic factors in breast cancer. Patient-related factors such as young age at diagnosis, obesity, and smoking behaviour may also modify disease outcome. Due to the absence of a unique definition for “young age breast cancer” and the resulting variation in disease management, findings on the association between young age and prognosis of breast cancer are controversial. Methods. This study included 1500 patients with a primary diagnosis of breast cancer in six Iranian hospitals from 5 provinces. We modelled the relative excess risk (RER) of breast cancer death to age at diagnosis and tumour characteristics. Results. Excess risks of death were observed for stage IV disease and poorly differentiated tumours: RER of 4.3 (95% CI: 1.05–17.65) and 3.4 (95% CI: 1.17–9.87), respectively. “Older” patients, particularly those aged 50 and over, presented more often with advanced and poorly differentiated tumours (P = 0.001). After adjustment for stage, histological grade, Her-2 expression, estrogen and progesterone receptors, and place of residency, breast cancer mortality was not significantly different across age groups. Conclusion. We conclude that there is no prognostic effect of age at diagnosis of breast cancer among breast cancer patients treated at cancer centres in different parts of Iran; young and relatively old women have similar risks of dying from breast cancer.
doi:10.1155/2012/517976
PMCID: PMC3512268  PMID: 23227345
21.  Postpartum mammary gland involution drives DCIS progression through collagen and COX-2 
Nature medicine  2011;17(9):1109-1115.
Prognosis of young women’s breast cancer is influenced by reproductive history. Women diagnosed within five years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors characterized by abundant fibrillar collagen, high COX-2 expression, and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high-risk for postpartum breast cancer would benefit from treatment with NSAIDs during postpartum involution.
doi:10.1038/nm.2416
PMCID: PMC3888478  PMID: 21822285
22.  Outcomes following local therapy for early-stage breast cancer in non-trial populations 
Recent studies suggest trends toward more mastectomies for primary breast cancer treatment. We assessed survival after mastectomy and breast-conserving surgery (BCS) with radiation for early-stage breast cancer among non-selected populations of women and among women similar to those in clinical trials. Using population-based data from Surveillance Epidemiology, and End Results cancer registries linked with Medicare administrative data from 1992 to 2005, we conducted propensity score analysis of survival following primary therapy for early-stage breast cancer, including BCS with radiation, BCS without radiation, mastectomy with radiation, and mastectomy without radiation. Adjusted survival was greatest among women who had BCS with radiation (median survival = 10.98 years). Compared with this group, mortality was higher among women who had mastectomy without radiation (median survival 10.04 years, adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI) = 1.14–1.23), mastectomy with radiation (median survival 10.02 years, HR = 1.20, 95% CI = 1.14–1.27), and BCS without radiation (median survival 7.63 years, HR = 1.81, 95% CI = 1.70–1.92). Among women representative of those eligible for clinical trials (age ≤70 years, Charlson comorbidity score = 0/1, and stage 1 tumors), there were no differences in survival for women who underwent BCS with radiation or mastectomy. In conclusion, after careful adjustment for differences in patient, physician, and hospital characteristics, we found better survival for BCS with radiation versus mastectomy among older early-stage breast cancer patients, with no difference in survival for BCS with radiation versus mastectomy among women representative of those in clinical trials. These findings are reassuring in light of recent trends towards more aggressive primary breast cancer therapy.
doi:10.1007/s10549-010-0865-4
PMCID: PMC2924956  PMID: 20376555
Breast cancer; Surgery; Outcomes; Mastectomy; Breast conservation
23.  Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study 
Introduction
Many women who survive breast cancer die of causes unrelated to their cancer diagnosis. This study was undertaken to assess factors that are related to breast cancer mortality versus mortality from other causes and to describe the leading causes of death among older women diagnosed with breast cancer.
Methods
Women diagnosed with breast cancer at age 66 or older between 1992 and 2000 were identified in the Surveillance, Epidemiology and End Results-Medicare linked database and followed through the end of 2005.
Results
A total of 63,566 women diagnosed with breast cancer met the inclusion criteria and were followed for a median of approximately nine years. Almost one-half (48.7%) were alive at the end of follow-up. Ages and comorbidities at the time of diagnosis had the largest effects on mortality from other causes, while tumor stage, tumor grade, estrogen receptor status, age and comorbidities at the time of diagnosis all had effects on breast cancer-specific mortality. Fully adjusted relative hazards of the effects of comorbidities on breast cancer-specific mortality were 1.24 (95% confidence interval (95% CI) 1.13 to 1.26) for cardiovascular disease, 1.13 (95% CI 1.13 to 1.26) for previous cancer, 1.13 (95% CI 1.05 to 1.22) for chronic obstructive pulmonary disease and 1.10 (95% CI 1.03 to 1.16) for diabetes. Among the total study population, cardiovascular disease was the primary cause of death in the study population (15.9% (95% CI 15.6 to 16.2)), followed closely by breast cancer (15.1% (95% CI 14.8 to 15.4)).
Conclusions
Comorbid conditions contribute importantly to both total mortality and breast cancer-specific mortality among breast cancer survivors. Attention to reducing the risk of cardiovascular disease should be a priority for the long-term care of women following the diagnosis and treatment of breast cancer.
doi:10.1186/bcr2901
PMCID: PMC3218953  PMID: 21689398
24.  Younger age as a prognostic indicator in breast cancer: A cohort study 
BMC Cancer  2011;11:383.
Background
The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort.
Methods
Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade.
Results
The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher HER2 over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and HER2 (p = 0.002) status and treatment received were independent predictors of OS
Conclusion
Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population.
doi:10.1186/1471-2407-11-383
PMCID: PMC3184119  PMID: 21871129
25.  Breast cancer associated with primary hyperparathyroidism: a nested case control study 
Clinical Epidemiology  2011;3:103-106.
Background:
Primary hyperparathyroidism (pHPT) is associated with an increased risk of developing breast cancer, but little is known about the underlying factors. The aim of this study was to compare women with a history of pHPT and a reference population in terms of standard factors predictive of prognosis and response to therapy for breast cancer.
Methods:
We analyzed data collected from the National Swedish Cancer Register and from two regional oncologic center registries. Seventy-one women with breast cancer and a history of parathyroid adenomectomy were compared with 338 matched controls with breast cancer only. Tumor size, stage, hormone receptor status, lymph node status, cause of death, and cumulative survival were analyzed.
Results:
The mean age was 69 ± 11 years (95% confidence interval [CI]: 68–70) in both groups and the mean time interval between the parathyroid surgery and breast cancer diagnosis was 91 ± 68 months (95% CI: 72–111). There were no differences between the two groups regarding size, stage, lymph node metastases, or survival, but none of the cases with a history of pHPT were found in Stage III or IV.
Conclusion:
In conclusion, factors predictive of prognosis and response to therapy in women with a history of pHPT and breast cancer are similar to those in breast cancer patients without pHPT.
doi:10.2147/CLEP.S17298
PMCID: PMC3072153  PMID: 21487450
breast cancer; primary hyperparathyroidism; prognostic factors

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