Breast Cancer Research and Treatment

, Volume 138, Issue 1, pp 241–248

Time-trends in survival in young women with breast cancer in a SEER population-based study

Authors

    • Division of Oncology, Department of MedicineWashington University in St. Louis School of Medicine
  • Adrienne Groman
    • Department of BiostatisticsRoswell Park Cancer Institute
  • Chi-Chen Hong
    • Department of Cancer Prevention and ControlRoswell Park Cancer Institute
  • Austin Miller
    • Department of BiostatisticsRoswell Park Cancer Institute
  • Shicha Kumar
    • Department of Surgical OncologyRoswell Park Cancer Institute
  • Ellis Levine
    • Department of MedicineRoswell Park Cancer Institute
  • Deborah Erwin
    • Division of Cancer Prevention and Population Sciences, Office of Cancer Health Disparities ResearchRoswell Park Cancer Institute
  • Christine Ambrosone
    • Department of Cancer Prevention and ControlRoswell Park Cancer Institute
Epidemiology

DOI: 10.1007/s10549-013-2425-1

Cite this article as:
Ademuyiwa, F.O., Groman, A., Hong, C. et al. Breast Cancer Res Treat (2013) 138: 241. doi:10.1007/s10549-013-2425-1

Abstract

Mortality improvements in young women with breast cancer (BC) may be attributable to treatment advances; screening likely plays a less significant role as mammography is not recommended <40. We examined time-trends in outcome in a cohort of young women. Our goal was to determine the contributions of treatment and screening to mortality improvements and evaluate whether differential outcomes by ER status exist. Using SEER, patients (73,447) were divided into three categories by diagnosis year (1990–1994, 1995–1999, 2000–2004) and also categorized as <40 or 40–50 years. Multivariate analysis was done to investigate the association of survival with time period for both age groups by ER status. Hazard ratios (HR) for mortality in women 40–50 with ER positive BC declined over time. With 1990–1994 as referent, the HR in 1995–1999 was 0.77 (0.69–0.86) and 0.65 (0.59–0.71) in 2000–2004 (p < 0.001). Women <40 with ER positive BC also had improvements over time. In ER negative patients, the degree of improvements over time was less than that seen in ER positive women. We report a survival disparity over time in young women by ER status. Patients with ER negative disease have not had the degree of improvements over time as seen in ER positive disease. Therefore, mortality improvements in young women with ER positive BC may be attributed to treatment advances with endocrine agents.

Keywords

Breast cancerYoung ageSurvivalTrends

Introduction

In the United States, approximately 27 % of either non-invasive or invasive breast cancers occur in women under 50 years of age [1]. Among adolescent and young adult women, breast cancer is the most frequently diagnosed malignancy [2]. Breast cancer in young women remains poorly understood and is believed to represent a more biologically aggressive disease with a higher frequency of adverse histopathologic characteristics and worse outcomes [3, 4]. These cancers are more likely to be high-grade, triple negative, HER2 positive, and have the presence of lymphovascular space invasion [59]. They are also more likely to be associated with a positive family history [10] and black race [11]. Young age also appears to be independently prognostic of a worse outcome compared to an older age at presentation [1214].

Improved breast cancer outcomes have been seen in recent years [1519], presumably due to widespread breast cancer screening and improved treatment strategies. Breast cancer mortality rates have decreased by 2.2 % each year from 2000 to 2009 for all ages combined [20]. Specifically, for women under the age of 50 years, death rates have decreased by 3 % per year as opposed to a yearly decrease of 1.9 % in women ≥50 years. The slower mortality gains in older women may be explained by a higher frequency of comorbidities, poorer utilization of screening mammograms, and a lower probability of receiving standard of care treatments [2123]. It is unclear if the more rapid gains in survival in younger women are due to screening or treatments. Since routine mammography is not generally recommended for women under the age of 40, it is reasonable to conclude that mortality improvements in this group are attributable to treatment advances with screening playing a less important role. Consequently, we sought to examine the time trends in breast cancer outcome, as well as presentation, in a population-based cohort of young women to determine the relative contributions of treatment and screening to improvements documented in the literature. Since patients with estrogen receptor (ER) negative breast cancer generally have a worse outcome than those with ER positive disease, we examined changes in outcome over time by ER status. In addition, we evaluated whether younger age remained prognostic for poorer outcome in this cohort.

Patients and methods

Study population

Data for this study were obtained from the Surveillance, Epidemiology and End Results (SEER) database which represents the largest population-based cancer registry in the United States. It covers 28 % of the population and captures 97 % of incident cancer cases in those regions participating in SEER [20]. The SEER registries collect information on demographics, primary tumor site and characteristics, first course of treatment, and survival. The SEER program started in 1973 and consequently provides the greatest longevity for cancer statistics. These analyses included records for females aged ≤50 years who had been diagnosed with breast cancer between 1990 and 2004. Our analysis had previously included women diagnosed up until 2008, but in order to have at least 5 year follow up on patients, those diagnosed after 2004 were subsequently excluded. Individuals who were diagnosed with breast cancer at death or autopsy only, had other first primary cancers, in situ disease, or did not have a record of ER, were excluded from this analysis (Fig. 1). After exclusions were applied, data on 73,447 women were available for analysis. The study was conducted under approval from the Roswell Park Cancer Institutional Review Board.
https://static-content.springer.com/image/art%3A10.1007%2Fs10549-013-2425-1/MediaObjects/10549_2013_2425_Fig1_HTML.gif
Fig. 1

Patients with breast cancer diagnosed between 1990 and 2004 that were included or excluded from the analytical cohort

Statistical analysis

Patient and tumor characteristics at the time of diagnosis were compared across three time periods (1990–1994, 1995–1999, and 2000–2004) using the Wilcoxon rank sum and Pearson χ2 tests for continuous and categorical variables, respectively. A cox proportional hazard model was used to evaluate time trends in overall survival (OS) by ER status among women <40 and those 40–50 years of age separately. The primary endpoint was OS. We censored patients at 5 years to keep follow up consistent. Patients alive at the date of last follow up were censored. We adjusted the analyses for race, tumor grade, histology, tumor size, progesterone receptor (PR) status, radiation, surgery, American Joint Committee on Cancer (AJCC) stage, and numbers of positive lymph nodes as these were considered confounding factors. Age, period of diagnosis, and ER status, and the two-way and three-way interaction terms were included in the model as explanatory variables. To evaluate a potential interaction between ER status and age, Kaplan–Meier (KM) estimates of survival were initially generated and a log-rank test was used to test for differences in OS by ER status and age-group. Cox proportional hazard models were subsequently used to calculate multivariate hazard ratios and 95 % CIs with adjustments and age, period of diagnosis, and ER status, and the two-way and three-way interaction terms were included in the model as explanatory variables. The Akaike information criterion (AIC) was used to determine the best model fit (smallest is best). The model with the smallest AIC was the model with two- and three-way interactions between age, period of diagnosis, and ER status. Four contrasts were implemented to determine the effect of period of diagnosis within the age-group and ER status categories. To evaluate time trends in breast cancer presentation, logistic regression analysis was used to generate odds ratios (OR) and 95 % CIs for developing AJCC stages I, II, III/IV breast cancer and breast cancers of varying tumor size across the time periods being examined for women <40, and for women age 40–50 years. As the SEER registries expanded during this study period, we performed a sensitivity analysis limiting the dataset to registries in existence during 1990–1994. The results did not differ from the entire dataset; thus, we present results of the larger dataset. All associations were considered statistically significant at an alpha <0.01 (p value 0.01). All statistical analyses were performed using the SAS statistical software package (version 9.3; SAS Institute, Inc., Cary, NC).

Results

Patient characteristics

Sixteen thousand two hundred and thirty six patients (22.1 %) were <40 years at diagnosis, and 57,211 (77.9 %) were 40–50 years. Fifty one thousand five hundred and thirty (70.2 %) of patients were ER positive, and 21,917 (29.8 %) were ER negative. Characteristics for the entire cohort are summarized in Table 1. Differences between patient characteristics by year of diagnosis were observed with respect to age, AJCC stage, ER status, and number of involved nodes. A progressively higher number of patients aged 40–50 were diagnosed from 1990 to 2004 (75.3, 77.5, and 78.9 %, respectively), while the number of younger patients <40 years, who were diagnosed, declined over time (24.7, 22.5, and 21.1 %). A lower frequency of patients diagnosed with four or more lymph nodes was observed from time periods 1990–2004 (16.8, 14.8, and 14.3 %, respectively). Differences between ER positive and negative patients were observed with respect to age, race, grade, stage, histology, number of involved nodes, and PR status (data not shown). A higher proportion of patients with ER negative disease were younger (p < 0.001), black (p < 0.001), and had tumors with higher grades (p < 0.001), ductal histology (p < 0.001), and negative PR (p < 0.001). The proportion of ER absent cases declined over time from 17.8 % in 1990–1994, 14.3 % in 1995–1999, and 12.1 % in 2000–2004 (Supplemental Table 1). This analysis is limited to only those patients with known ER status.
Table 1

Patients’ characteristics by year of diagnosis

Variable

1990–1994

1995–1999

2000–2004

p value

N

%

N

%

N

%

12,958

17.6

18,866

25.7

41,623

56.7

<0.001

Age

 <40

3,197

24.7

4,250

22.5

8,789

21.1

<0.001

 40–50

9,761

75.3

14,616

77.5

32,834

78.9

 

Race

 White

10,317

79.6

14,798

78.4

32,714

78.6

<0.001

 Black

1,354

10.4

1,860

9.9

4,490

10.8

 

 Other

1,287

9.9

2,208

11.7

4,419

10.6

 

ER status

 Positive

8,462

65.3

12,965

68.7

30,103

72.3

<0.001

 Negative

4,496

34.7

5,901

31.3

11,520

27.7

 

PR status

 Positive

7,997

61.7

11,791

62.5

26,652

64.0

<0.001

 Negative

4,520

34.9

6,412

34.0

14,040

33.7

 

AJCCa stage

 I

5,095

39.3

7,785

41.3

16,561

39.8

<0.001

 II

6,418

49.5

9,137

48.4

20,395

49.0

 

 III/IV

1,186

9.2

1,566

8.3

4,316

10.4

 

 Unknown

259

2.0

378

2.0

351

0.8

 

Grade

 I

924

7.1

2,240

11.9

5,773

13.9

<0.001

 II

3,631

28.0

6,603

35.0

15,145

36.4

 

 III/IV

5,335

41.2

8,579

45.5

18,625

44.8

 

 Unknown

3,068

23.7

1,444

7.7

2,080

5.0

 

Nodes involved

 0

7,089

58.3

10,516

59.4

22,883

56.8

<0.001

 1–3

3,023

24.9

4,565

25.8

11,647

28.9

 

 4–7

1,096

9.0

1,426

8.0

3,225

8.0

 

 >7

942

7.8

1,210

6.8

2,559

6.3

 

Surgery

 BCSb

6,216

48.0

10,898

57.8

23,093

55.5

<0.001

 Mastectomy

6,742

52.0

7,968

42.2

18,530

44.5

 

Status

 Alive

11,097

85.6

16,720

88.6

37,637

90.4

<0.001

 Dead

1,861

14.4

2,146

11.4

3,986

9.6

 

aAmerican Joint Committee on Cancer

bBreast conserving surgery

Time trends in mortality

At a median follow up of 60 months, a total of 2,428 (14.9 %) women <40 years and 5,565 (9.7 %) women 40–50 years had died. Overall, 24.2 % of the population did not reach 5 years of follow up. Specifically, in 1990–1994, 14.8 % did not reach 5 years of follow up; in 1995–1999, the proportion was 12.1; and 32.6 % in 2000–2004. Multivariate adjusted hazard ratio for mortality (with follow up censored at 5 years) in women in both age groups with either ER positive or negative breast cancer declined over time (Table 2). Comparing each period to 1990–1994, the HR for mortality in ER positive women 40–50 years diagnosed in 1995–1999 was 0.77 (0.69–0.86) and 0.65 (0.59–0.71) in 2000–2004, representing a 23 and 35 % decrease from baseline, respectively. Those <40 years with ER positive breast cancer also had improvements in mortality over time. Although mortality improvements were seen in ER negative disease, those improvements were to a lesser degree than those seen in ER positive disease. Relative to 1990–1994, in those 40–50, the HR for mortality in 1995–1999 was 0.98 (0.88–1.09) and 0.90 (0.82–0.99) in 2000–2004, representing only a 2 and 10 % decrease from baseline.
Table 2

Mortality risk over time by age group and ER status

Variable

5 year OS (95 % CI)

10 year OS (95 % CI)

1990–1994

1995–1999

2000–2004

p value

Events

Prsn-yrs*

HR

95 % CI

Events

Prsn-yrs

HR

95 % CI

Events

Prsn-yrs

HR

95 % CI

ER positive

 40–50

0.94 (0.94–0.94)

0.85 (0.85–0.86)

616

31,726

Ref

678

50,744

0.77

0.69–0.86

1,285

115,625

0.65

0.59–0.71

<0.001

 <40

0.89 (0.89–0.90)

0.77 (0.76–0.78)

288

8,577

Ref

270

11,966

0.74

0.63–0.88

494

25,544

0.60

0.52–0.70

<0.001

ER negative

 40–50

0.81 (0.80–0.81)

0.74 (0.73–0.74)

616

14,099

Ref

829

18,606

0.98

0.88–1.09

1,541

35,900

0.90

0.82–0.99

0.033

 <40

0.79 (0.78–0.80)

0.72 (0.71–0.73)

341

5,888

Ref

369

7,717

0.80

0.69–0.93

666

14,059

0.74

0.65–0.84

<0.001

* Person-years. Analyses adjusted for race, tumor grade, histology, number of lymph nodes involved, PR status, receipt of radiation, surgery type, and stage

Time trends in breast cancer characteristics

A 1.3-fold increase in the odds of presenting with stage I breast cancer was seen in women aged 40–50 years comparing the two latter time periods to 1990–1994. Similarly, in the same age group, there was a higher likelihood of presenting with a tumor ≤1 cm in the latter time periods versus 1990–1994. In women <40 years at diagnosis, there was a higher likelihood of presenting with stage I disease in 1990–1994 versus the latter two periods; and a higher likelihood (OR 1.47) of presenting with stage III/IV disease was seen in 2000–2004 compared to that of 1990–1994 (Table 3).
Table 3

Trends in breast cancer characteristics over time by age

Variable

1990–1994

1995–1999

2000–2004

p value

%a

ORb (95 % CI)

%

OR (95 % CI)

%

OR (95 % CI)

AJCC stage

 <40 years

  I

32

Ref

34

0.84 (0.77–0.93)

31

0.74 (0.68–0.80)

<0.001

  II

55

Ref

55

1.16 (1.06–1.27)

55

1.17 (1.08–1.27)

<0.001

  III/IV

11

Ref

9

1.00 (0.86–1.16)

13

1.47 (1.30–1.66)

<0.001

 40–50 years

  I

42

Ref

44

1.36 (1.29–1.43)

42

1.30 (1.24–1.36)

0.131

  II

48

Ref

47

0.82 (0.78–0.87)

47

0.85 (0.81–0.89)

<0.001

  III/IV

9

Ref

8

0.80 (0.72–0.87)

10

0.97 (0.89–1.05)

<0.001

Tumor size

 <40 years

  ≤1 cm

8

Ref

9

0.90 (0.77–1.06)

11

1.08 (0.94–1.24)

<0.001

  >1 to <3 cm

33

Ref

34

0.91 (0.83–1.00)

31

0.78 (0.72–0.85)

<0.001

  >3 to ≤5 cm

48

Ref

47

1.13 (1.03–1.24)

47

1.10 (1.02–1.19)

0.098

  >5 cm

11

Ref

10

1.07 (0.92–1.25)

12

1.37 (1.21–1.55)

<0.001

 40–50 years

  ≤1 cm

12

Ref

14

1.60 (1.47–1.73)

17

1.92 (1.80–2.06)

<0.001

  >1 to <3 cm

38

Ref

39

1.16 (1.10–1.23)

37

1.07 (1.02–1.12)

<0.001

  >3 to ≤5 cm

42

Ref

40

0.77 (0.73–0.81)

39

0.73 (0.70–0.77)

<0.001

  >5 cm

8

Ref

8

0.77 (0.70–0.85)

8

0.85 (0.78–0.92)

<0.001

Analysis not shown for 71 women <40 years and 188 women 40–50 years with unknown staging. Analysis adjusted for race, grade, histology, number of involved lymph nodes, PR status, receipt of radiation, surgery type, and stage

aPercentage of breast cancers in that category

bOdds ratio

Impact of age on outcomes

The 5-year and 10-year OS rates were 89 and 80 % for all patients; 82 and 71 % for women <35 years, 86 and 76 % for 35–39 years, 89 and 81 % for 40–44 years, and 90 and 82 % for women aged 45–50 at diagnosis. Median OS was not reached in any category. Unadjusted KM estimates indicated differences in OS by age group and ER status (Fig. 2). Although similar results were seen for both ER positive and negative patients, among ER negative patients, there was markedly less variation in 5 year OS by age than that seen in ER positive patients; 79–81 % versus 89–94 %, respectively (Table 2). The worst survival outcomes were seen in those <35 years with ER negative disease.
https://static-content.springer.com/image/art%3A10.1007%2Fs10549-013-2425-1/MediaObjects/10549_2013_2425_Fig2_HTML.gif
Fig. 2

Kaplan–Meier estimates of overall survival. All patients by age. All ER positive patients by age. All ER negative patients by age

Cox regression analysis demonstrated the association of higher grade disease, PR negativity, black race, absence of radiation, younger age, and lymph nodal involvement as independent prognostic factors for 5 year survival (Table 4). Age was not associated with OS in ER negative patients in multivariable analysis (data not shown).
Table 4

Multivariate model results for 5 year survival

Variable

Hazard ratio

95 % CI

p

Age

 <40

Referent

  

 40–50

1.31

1.28–1.34

<0.0001

Grade

 I

Referent

  

 II

1.97

1.67–2.31

<0.0001

 III

3.07

2.62–3.59

 

 IV

3.42

2.83–4.12

 

Race

 White

Referent

  

 Black

1.57

1.49–1.66

<0.0001

 Other

0.99

0.91–1.07

 

Radiation

 No

Referent

  

 Yes

0.79

0.75–0.83

<0.0001

Histology

 IDC

Referent

  

 ILCa

0.74

0.65–0.84

<0.0001

 Mixed

0.94

0.86–1.03

 

 Other

0.57

0.49–0.66

 

Surgery

 BCSb

Referent

  

 Mastectomy

1.04

0.98–1.09

0.188

Diagnosis year

 1990–1994

Referent

  

 1995–1999

1.48

1.44–1.52

0.306

 2000–2004

1.81

1.77–1.85

 

ER

 Positive

Referent

 

<0.0001

 Negative

1.45

1.41–1.49

PR

 Negative

Referent

  

 Positive

0.71

0.66–0.76

<0.0001

Lymph nodes

 0

Referent

  

 1–3

1.65

1.53–1.78

<0.0001

 4–7

2.63

2.41–2.86

 

 >7

4.12

3.83–4.51

 

Analyses adjusted for age at presentation, race, tumor grade, histology, number of lymph nodes involved, ER, PR status, receipt of radiation, surgery type, and diagnosis year

aInvasive lobular carcinoma

bBreast conserving surgery

Discussion

In this study, we aimed to determine the relationship between age and time trends in survival and breast cancer presentation in a population-based cohort of young women stratifying by ER status. To achieve this aim, we analyzed 73,447 patients aged 50 years and under from the SEER database. Several findings emerged. First, our data clearly demonstrate that improvements in breast cancer outcome over time have occurred in women ≤ 50 years with ER positive disease, with mortality reductions being similar in women aged 40-50 as well as younger than 40 years. Although improvements in women with ER negative breast cancer were also seen, the degrees of improvements were much less than those observed in women with ER positive breast cancer. To our knowledge, no other study has reported similar findings. Results of recent epidemiologic data showing improvements over time for all ages [20] are likely driven by the much larger proportion of ER positive breast cancer that occurs. Several possible explanations for our findings exist. The greater degree of improvements over time in ER positive women may be attributable to treatment with endocrine therapies with screening playing a less important role. This is further buttressed by the observation that mortality reductions were also seen in ER positive women younger than 40 years, a group that is not likely to undergo routine screening. In fact, although it did not focus specifically on patients with ER positive disease, a study evaluating trends in breast cancer mortality in several European countries demonstrated reductions in breast cancer deaths of up to 16–29 % between 1989 and 2006 [24]. The authors concluded that since the European countries studied had wide differences in screening practices, the observed similarities in mortality reduction were likely attributable to improvements in treatment and the healthcare systems and less likely attributable to screening. The degree of improvements in patients with ER positive disease seen over time could also be related to the release of the Early Breast Cancer Trialists’ Collaborative Group overview analysis showing a substantial benefit from the use of 5 years of tamoxifen in premenopausal ER positive patients, which rapidly became the new standard of care. Another plausible and contributory explanation may be that women with ER negative disease may derive less survival benefits from screening mammography than those with ER positive disease. It is noteworthy that studies have shown that women with ER negative disease tend to have breast cancers diagnosed as interval cancers [25, 26], likely due to the rapid proliferation characteristics such tumors possess. With respect to the presentation of breast cancer over time, our data showed that women <40 years, who are statistically more likely to have ER negative disease, have actually presented with more advanced disease over time. One should not conclude, however, that mammograms have no role in detecting breast cancer in ER negative patients as determination of the ER status is done after diagnosis. Women who may be at an elevated risk for ER negative breast cancer, such as those with a strong family history, BRCA mutation carriers, or those of African descent, may require more intense screening with the use of magnetic resonance imaging in combination with mammography. In addition, as slower survival gains have been made in this cohort of women, improved adjuvant therapies need to be developed.

We also observed an increasing proportion of breast cancer over time in women aged 40–50 years compared with women <40 years. Among all women in this study, the proportion of those aged 40–50 years and diagnosed during 1990 and 1994 was 75.3%; 77.5 % between 1995 and 1999; and 78.9 % between 2000 and 2004. This is likely due to the increasing usage of screening mammograms in this age group over time. This is also supported by the increased probability of being diagnosed with earlier disease observed in this age group over time.

Lastly, unlike ER positive breast cancer patients, younger age did not appear to be associated with OS after controlling for multiple factors in patients with ER negative disease. There was much less 5 year OS variation by age in ER negative patients than that seen in ER positive patients, suggesting a poorer prognosis irrespective of age. The association between poorer breast cancer outcomes and younger age may be stronger for ER positive breast cancers where a plausible explanation for this relationship exists. It is known that younger premenopausal women are more likely to regain ovarian function after cytotoxic chemotherapy than older women, and those who do regain this function have an inferior outcome compared to those who do not [27, 28]. This may be less important in ER negative breast cancers that are believed to be hormone-independent. The other consideration is that ER negative breast cancers represent a more biologically heterogeneous disease than ER positive breast cancer and thus the contribution of younger age or other factors as negative prognostic indicators may not be as apparent. Indeed, we had previously reported on the absence of a significant relationship between obesity and clinical outcomes in patients with triple negative breast cancers [29].

Although these data provide a population-based representation of trends in breast cancer outcome and presentation by age, our findings must be interpreted in light of several limitations. As SEER does not collect detailed information on treatment, we were not able to control for receipt of chemotherapy. It is possible that patients in the younger age group and/or with ER negative disease in this study were more likely to be treated with chemotherapy as opposed to older patients or those with ER positive breast cancer. If that was the circumstance, one may have expected improved outcomes to be seen in those more likely to receive chemotherapy. Another key variable for which we could not account due to similar data collection reasons was HER2 status. In addition, we were not able to report on breast cancer-specific survival, as the reliability of cause of death coding by SEER has been questioned. During a preliminary analysis of this dataset, only 1.9 % of the patients was coded with a breast cancer death. This is an underrepresentation of the true numbers of breast cancer deaths particularly in a younger age group that usually does not have multiple competing causes of deaths. Therefore, as this age group is not one that is usually fraught with comorbidities, OS represents an accurate estimation of the burden of cancers in this group. Analyzing survival data over time can be subject to problems associated with stage migration, due to more sophisticated diagnostic techniques. Patients in a more recent time period may be more likely to present with more advanced disease due to improved detection of smaller metastasis. Indeed, our data did show that the proportion of those with stage III/IV disease did increase slightly from 9.2 % in 1990–1994 to 10.4 % in 2000–2004. Similarly, patients in the more distant past may be misclassified as having earlier stage breast cancer with a worse outcome due to the fact that they actually had later stage disease which was unable to be detected. However, there is no biological reason as to why this would differ by age group. Approximately 25 % of our study population did not reach 5 years of follow up; the proportion not reaching 5 years follow up was higher in the most recent time period. This potentially introduces a source of bias to the results. Lastly, we acknowledge that missing data can bias the analysis of registry data. Our analysis showed that the proportion of missing ER data was slightly higher in the earlier time periods. While several statistical methods to account for missing data do exist, we are hesitant to employ such techniques to reassign unknown ER status which is a key classifier of breast cancers. Therefore, we included only those patients with known ER status.

In summary, this study extends the literature on trends in breast cancer survival in young women by reporting a disparity by ER status. As we have demonstrated that greater mortality improvements over time have occurred in women ≤50 years with ER positive disease, the extent to which improvements have occurred in women with ER negative disease remains an open question. While it is reassuring that improvements in breast cancer outcome have occurred over time for some young women, further research is needed to fully understand breast cancer in younger women particularly for those who are afflicted with ER negative disease. We suggest increased attempts to involve this group of women in clinical trials.

Conflict of interest

None.

Supplementary material

10549_2013_2425_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 48 kb)

Copyright information

© Springer Science+Business Media New York 2013