Breast Cancer Among the Oldest Old: Tumor Characteristics, Treatment Choices, and Survival

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Impact Factor: 18.43 · DOI: 10.1200/JCO.2009.25.9796 · Source: PubMed
Abstract
PURPOSE Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. PATIENTS AND METHODS We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, > or = 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer-related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age > or = 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age > or = 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). CONCLUSION Women age > or = 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit.

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Available from: Rebecca A Silliman, Apr 07, 2015
Breast Cancer Among the Oldest Old: Tumor
Characteristics, Treatment Choices, and Survival
Mara A. Schonberg, Edward R. Marcantonio, Donglin Li, Rebecca A. Silliman, Long Ngo,
and Ellen P. McCarthy
See accompanying editorial on page 1975 and article on page 2046
From the Division of General Medicine
and Primary Care, Department of Medi-
cine, Harvard Medical School, Beth
Israel Deaconess Medical Center; Geri-
atrics Section, Boston University
Schools of Medicine and Public Health,
Boston University Medical Center,
Boston, MA.
Submitted September 2, 2009;
accepted December 4, 2009; published
online ahead of print at www.jco.org on
March 22, 2010.
Supported by Grant No. K23AG028584
from the National Institutes of Health,
National Institute on Aging, and a Soci-
ety of General Internal Medicine, Asso-
ciation of Chiefs of General Internal
Medicine, Association of Specialty
Professors T. Franklin Williams Scholars
Award in Geriatrics, and a 2006 Hart-
ford Geriatrics Health Outcomes
Research Scholars Award.
Presented in part at the 32nd Annual
Meeting of the Society of General Inter-
nal Medicine, May 13-16, 2009, Miami
Beach, FL, and the 2009 Annual Meet-
ing of the American Geriatrics Society,
April 29-May 2, 2009, Chicago, IL.
Authors’ disclosures of potential con-
flicts of interest and author contribu-
tions are found at the end of this
article.
Corresponding author: Mara A. Schonberg,
MD, MPH, Beth Israel Deaconess
Medical Center, 1309 Beacon, Office
202, Brookline, MA 02446; e-mail:
mschonbe@bidmc.harvard.edu.
© 2010 by American Society of Clinical
Oncology
0732-183X/10/2812-2038/$20.00
DOI: 10.1200/JCO.2009.25.9796
ABSTRACT
Purpose
Few data are available on breast cancer characteristics, treatment, and survival for women age 80
years or older.
Patients and Methods
We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992
to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery
[BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years
or older (80 to 84, 85 to 89, 90 years) with stage I/II breast cancer compared with young-
er women (age 67 to 79 years). We used Cox proportional hazard models to examine the
impact of age on breast cancer–related and other causes of death. Analyses were performed
within stage, adjusted for tumor and sociodemographic characteristics, treatments received,
and comorbidities.
Results
In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor
characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS
alone increased with age, especially after age 80. The risk of dying from breast cancer increased
with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from
breast cancer for women age 90 years compared with women age 67 to 69 years was 2.6
(range, 2.0 to 3.4). Types of treatments received were significantly associated with age and
comorbidity, with age as the stronger predictor (26% of women age 80 years without
comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years).
Conclusion
Women age 80 years have breast cancer characteristics similar to those of younger women yet
receive less aggressive treatment and experience higher mortality from early-stage breast cancer.
Future studies should focus on identifying tumor and patient characteristics to help target
treatments to the oldest women most likely to benefit.
J Clin Oncol 28:2038-2045. © 2010 by American Society of Clinical Oncology
INTRODUCTION
Women age 80 years and older are the fastest
growing segment of the US population, and breast
cancer is relatively common among these women
with nearly 400 cases per 100,000 women.
1
De-
spite the high incidence, little is known about
breast cancer characteristics, treatment choices,
and survival among the oldest women. These data
are important for decision making around breast
cancer detection and care. Few randomized con-
trolled trials that evaluated the effectiveness of
breast cancer treatments included women age 80
years or older, and most observational studies
were limited by small sample sizes in this age
range.
2-4
Studies using the Surveillance, Epidemi-
ology and End Results (SEER) -Medicare data set
have examined the effectiveness of radiation treat-
ment and chemotherapy among older women with
breast cancer.
5-8
However, these studies consistently
exclude women with missing stage and those with-
out a histologic diagnosis and/or known hormonal
receptivity. Meanwhile, women age 80 years or older
are most likely to fall into these categories.
2,4,9-12
Missing data may be one reason that studies differ
on whether elderly women present with higher
stage disease but with less aggressive tumors than
younger women.
2,13,14
JOURNAL OF CLINICAL ONCOLOGY
ORIGINAL REPORT
VOLUME 28 NUMBER 12 APRIL 20 2010
2038 © 2010 by American Society of Clinical Oncology
Page 1
Although studies consistently show that older women are under-
treated for breast cancer, the impact of undertreatment on breast
cancer survival among older women remains controversial. Gadjos et
al
3
found that rates of recurrence were not increased when under-
treated women (older than 70 years) were compared with convention-
ally treated patients, while others have found that undertreatment is
associated with recurrence and decreased survival.
2,15,16
The purpose of this study was to examine variations in breast
cancer tumor characteristics, initial treatments received, and survival
among women age 80 to 84, 85 to 89, and 90 years with early-stage
(stage I or II) breast cancer compared with younger women (age 67 to
79 years).
PATIENTS AND METHODS
We used data from the National Cancer Institute’s linked SEER-Medicare data
set. Since 1992, SEER has included 11 population-based tumor registries in the
metropolitan areas of San Francisco/Oakland, Detroit, Atlanta, and Seattle;
Los Angeles County; the San Jose–Monterey area; and the states of Connecti-
cut, Iowa, New Mexico, Utah, and Hawaii.
17
These areas cover approximately
14% of the US population.
18
We identified all women age 67 years or older
newly diagnosed with breast cancer or ductal carcinoma in situ between 1992
and 2003, excluding those diagnosed on death certificate or at autopsy
(n 102,184). We then excluded women diagnosed with a second cancer
within 12 months after their primary breast cancer diagnosis because health
care claims cannot reliably discriminate between procedures performed for
the index cancer versus the second cancer (100,404 remaining). We further
excluded women who had Medicare-managed care insurance within 2 years
before through 1 year after diagnosis because their claims data are incomplete
(75,286 remaining), and we further excluded women with gaps in their Medi-
care coverage (66,951 remaining).
We then considered excluding women missing data on American Joint
Committee on Cancer (AJCC) Staging 3rd edition (13.5% overall or 19% of
women age 80 to 89 years and 39.5% of women age 90 years), women with
a history of non-breast cancer (8.7%), and women without a histologic diag-
nosis (3.1%). However, when we considered these three exclusions together,
21.9% of our sample would be excluded, including 48.7% of women age 90
years (Appendix Table A1, online only). Since our study focused on breast
cancer characteristics among the oldest women, we chose not to make these
exclusions. Instead, we constructed an algorithm using data available on tu-
mor characteristics (extent, number of positive lymph nodes, lymph node
invasion, tumor size, and histology) to impute stage for women with missing
stage (Appendix A, online only). After imputing stage, only 1.4% of women
were still missing stage data. For cases with both known and imputed (AJCC
3rd edition) stage, we tested the extent to which the two measures agreed
beyond chance using a two-sided
statistic. Because of the observed excellent
agreement (the two-sided
statistic was 0.997), we used imputed stage for
those women with missing stage in our primary analyses. Our sample included
49,616 women with known or imputed stage I or II disease.
Tumor Characteristics
From SEER, we obtained data on tumor size, regional lymph node
involvement, tumor grade, histology, estrogen receptivity (ER), and proges-
terone receptivity. Variable definitions can be found in Appendix B (on-
line only).
Treatments
We used data from both SEER and Medicare claims to classify initial
treatment with surgery or radiation therapy (RT). We considered women to
have received surgical and/or RT if reported in SEER or if there were Medicare
claims for these treatments within 12 months following diagnosis. We catego-
rized initial treatment as mastectomy, breast-conserving surgery (BCS) plus
RT, BCS alone, or no initial surgery. We used Medicare claims to identify
receipt of chemotherapy within 12 months following diagnosis among women
with ER-positive and lymph node–positive disease, since this population is
thought to derive benefit.
6,7,19
Women were classified as having any claim
versus no claim for chemotherapy (Appendix B).
Survival Outcomes
Survival time was measured from the patient’s date of diagnosis until
death or December 31, 2005, whichever came first. SEER tracks vital status
annually, and death certificates are used to capture underlying cause of death
(Appendix B).
Covariates
Patient characteristics included race/ethnicity, marital status,
SEER registry, metropolitan versus nonmetropolitan residence, and
year of diagnosis.
6-8
Because SEER-Medicare data do not provide individual-
level data on income and/or education, we used census tract data and substi-
tuted ZIP code–level data when census tract data were not available.
20
We
grouped median household income and percentage of adults with less than a
high school education into quintiles within registry. We defined comorbidity
using Klabunde’s modification of the Charlson comorbidity index (CCI).
21
Analyses
We examined sociodemographic and tumor characteristics by age at
diagnosis (67 to 69, 70 to 74, 75 to 79, 80 to 84, 85 to 89, and 90 years), and
we examined receipt of treatment by age at diagnosis and stage using the
Mantel-Haenszel test of trend. Because of the large sample size, we knew a
priori that even small differences in characteristics among age groups would
achieve statistical significance; however, we were most interested in trends by
age. We additionally examined the proportion of women who were treated
with BCS and RT or mastectomy since these treatments are considered stan-
dard and equally effective for early-stage breast cancer.
22
Using multinomial
logistic regression, we examined the effect of age and comorbidity on receipt of
treatments for stage I and II disease separately, adjusting for sociodemograph-
ics, tumor characteristics, and year of diagnosis. Since few women did not
undergo surgery (n 843; 1.7%), we did not include “no initial surgery” as a
treatment option in these analyses. A category of “missing” was included for
each covariate in the models.
To determine the impact of age at diagnosis on breast cancer death, we
conducted multivariable Cox proportional hazards regression adjusting for
sociodemographic and tumor characteristics, year of diagnosis, initial treat-
ments received, and comorbidity. We censored observations of women alive
when follow-up ended. We further tested for interactions between treatment
and age at diagnosis on breast cancer mortality. To test for residual confound-
ing, we examined the impact of initial treatment on non-breast cancer survival
and overall survival.
23
We present the results for non-breast cancer survival
since results were similar. We further examined the impact of chemotherapy
on breast cancer survival for the subset of women with ER-negative and lymph
node–positive tumors adjusting for all covariates.
We performed sensitivity analyses to examine the robustness of our
findings. First, we reassessed the impact of treatment on breast cancer survival
with propensity score methods, using the “Greedy” match SAS macro
24
to
minimize bias related to the nonrandom assignment of treatment. Next, we
limited our sample to women with known AJCC stage, known histology, and
those without a history of cancer. All statistical analyses used SAS version 9.1
(SAS Institute, Cary, NC). The institutional review board approved this study.
RESULTS
Sample Characteristics
Of the 49,616 women included in our final study population,
28,897 had stage I and 16,582 had stage II disease. We used imputed
stage for 6,571 women (13.2%). Table 1 displays sociodemographic
and tumor characteristics by age at diagnosis. Women age 80 years
(21.8%) were more likely than women age 67 to 79 years (15.0%) to
have a CCI of 2.
Breast Cancer Among the Oldest Old
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Table 1. Sample and Tumor Characteristics of Older Women With Stage I and II Breast Cancer
Characteristic
Patients in Age Group (years)
P
67-69 70-74 75-79 80-84 85-89 90
No. % No. % No. % No. % No. % No. %
No. of patients 7,437 13,774 12,757 8,908 4,707 2,033
Patient characteristics
Race/ethnicity
Non-Hispanic white 85.6 86.3 88.3 90.1 91.3 90.1 .001
Non-Hispanic black 5.1 5.3 5.1 4.4 4.6 5.1
Hispanic 3.8 3.5 2.6 2.5 2.0 2.6
Other 5.6 4.9 4.0 3.0 2.2 2.2
Marital status
Currently married 60.3 53.5 42.3 28.7 16.5 7.4 .001
Not married 37.4 44.4 55.2 68.1 80.1 88.2
Unknown 2.3 2.3 2.6 3.2 3.5 4.4
Charlson comorbidity index
0 67.6 64.3 59.3 56.1 50.9 48.7 .001
1 17.2 19.3 21.1 21.9 24.4 26.0
2 11.2 13.6 17.6 20.1 23.1 24.0
Unknown 4.0 2.8 2.0 1.9 1.7 1.3
Year of diagnosis
1992-1995 38.9 36.6 32.8 33.7 34.2 34.9 .001
1996-1999 31.9 34.0 33.9 32.5 32.8 32.1
2000-2003 29.2 29.4 33.3 33.8 33.0 33.0
Quintiles of median income for area of
residence (n 49,361)
1st 21.4 21.2 21.6 23.3 25.6 27.9 .001
2nd 20.1 20.7 21.3 22.3 21.6 21.0
3rd 19.2 19.5 19.9 19.4 19.6 19.8
4th 18.7 19.2 19.6 17.8 17.9 16.4
5th 20.7 19.4 17.7 17.3 15.4 14.9
Quintiles of education ( 12 years) for those
age 25 in area of residence (n 49,362)
1st 20.3 20.6 20.9 20.9 22.1 23.6 .001
2nd 20.4 19.8 20.4 21.0 21.2 20.7
3rd 19.5 20.0 19.4 19.5 19.9 20.4
4th 19.6 19.5 19.8 20.3 19.5 18.5
5th 20.2 20.1 19.5 18.4 17.3 16.8
Status of residence
Metropolitan 91.1 91.7 91.2 90.7 89.6 87.7 .001
Nonmetropolitan 8.9 8.3 8.8 9.3 10.4 12.3
Tumor characteristics
Stage II 34.8 34.0 35.1 37.2 42.3 53.0 .001
Tumor size, cm
1 34.7 34.2 32.4 28.4 21.5 12.5 .001
1to 2 38.5 39.3 39.5 39.1 38.2 35.0
2to 5 22.2 21.8 23.8 27.8 34.4 44.9
5 0.9 0.9 1.1 1.1 1.8 3.2
Unknown 3.7 3.9 3.3 3.5 4.0 4.5
Histology
Ductal 79.1 78.5 77.8 77.8 77.4 72.9 .001
Lobular 8.0 7.9 8.1 7.1 6.9 5.6
Mucinous 3.5 4.4 4.7 5.5 5.5 6.5
Other 8.5 8.4 8.3 8.2 7.9 9.3
Unknown 0.7 0.9 1.0 1.4 2.3 5.8
No. of positive lymph nodes
None examined 11.0 15.3 21.1 34.1 50.1 71.5 .001
None positive 68.4 64.9 60.5 49.3 35.9 16.8
1-3/unknown 14.3 13.7 12.7 11.4 9.1 7.2
4-9 3.9 3.7 3.4 3.3 3.0 2.5
10 1.4 1.4 1.4 1.2 0.9 0.9
Unknown 1.1 1.1 1.0 0.8 1.0 1.1
(continued on following page)
Schonberg et al
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OURNAL OF CLINICAL ONCOLOGY
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Tumor Characteristics
Among women with known tumor grade and progesterone
receptivity status, there were no statistically significant differences
by age. Differences in ER positivity by age were small ( 5%
differences among those with known receptor status). Tumor size
increased with age, and the increase was more dramatic after age 80
years. Similarly, the number of women who did not have lymph
nodes examined increased with age, and the rate of increase was
more dramatic after age 80. Among women who had their lymph
nodes examined, those age 80 years were disproportionately
more likely to have positive nodes detected than women age 67 to
79 years.
Initial Treatments
Nearly all women (98.3%) received some surgery for early-
stage breast cancer. For women with stage I disease, treatment with
BCS RT declined with age, particularly after age 80 (Fig 1).
Mastectomy was the most common treatment among women age
80 to 84 years. Almost all (91.7%) women age 67 to 79 years with
stage I disease received mastectomy or BCS RT compared with
66.8% of women age 80 years. Among women with stage II
disease, mastectomy was the most common treatment regardless of
age (Fig 2). However, BCS RT declined with age. Nearly all
women age 66 to 79 years with stage II disease (94.5%) received
BCS RT or mastectomy compared with 76.1% of women age
80 years. Among women with ER-negative, lymph node–
positive disease, receipt of chemotherapy declined significantly with
age (Fig 3).
In multinomial logistic regression, women age 80 years were
significantly more likely than women age 67 to 79 years to be treated
with mastectomy (odds ratio [OR], 2.1; 95% CI, 2.0 to 2.2) or with
BCS alone (OR, 4.2; 95% CI, 4.0 to 4.6) compared with BCS RT.
Table 1. Sample and Tumor Characteristics of Older Women With Stage I and II Breast Cancer (continued)
Characteristic
Patients in Age Group (years)
P
67-69 70-74 75-79 80-84 85-89 90
No. % No. % No. % No. % No. % No. %
Among women with examined nodes 6,549 11,542 9,972 5,805 2,313 564
Positive nodes 22.4 22.5 22.6 24.5 26.9 39.4 .001
Tumor grade
1 (Well differentiated) 18.6 21.0 20.9 19.9 18.7 15.5 .001
2 (Moderately differentiated) 39.4 39.2 40.1 40.3 38.7 37.6
3 (Poorly differentiated) 26.4 24.4 23.9 24.6 25.4 26.6
4 (Undifferentiated) 2.0 1.7 1.7 1.6 1.9 1.8
Unknown 13.6 13.7 13.4 13.6 15.7 18.5
Among women with known tumor grade 6,429 11,881 11,045 7,693 3,988 1,657
1 (Well differentiated) 21.6 24.3 24.2 23.0 22.1 19.1 .21
2 (Moderately differentiated) 45.6 45.4 46.3 46.7 45.7 46.2
3 (Poorly differentiated) 30.6 28.3 27.6 28.5 30.0 32.6
4 (Undifferentiated) 2.3 2.0 2.0 1.8 2.2 2.2
Estrogen receptor status
Positive/borderline 67.3 68.2 70.0 68.2 65.8 61.3 .001
Negative 15.0 13.7 12.0 11.7 10.6 11.0
Unknown/not tested 17.8 18.1 18.0 20.1 23.6 27.7
Among women with known estrogen receptor
status
6,116 11,284 10,462 7,122 3,595 1,470 .001
Positive/borderline 81.8 83.3 85.4 85.4 86.1 84.8
Negative 18.2 16.7 14.7 14.6 13.9 15.2
Progesterone receptor status
Positive/borderline 56.6 57.4 58.4 56.2 53.4 51.1 .001
Negative 24.0 23.0 22.1 22.4 21.7 19.9
Unknown/not tested 19.4 19.6 19.5 21.4 25.0 29.0
Among women with known progesterone
receptor status
5,992 11,080 10,272 7,004 3,531 1,445 .05
Positive/borderline 70.2 71.4 72.6 71.5 71.1 71.9
Negative 29.8 28.7 27.4 28.5 28.9 28.1
Vital status at end of follow-up period (12/31/
2005)
Alive 74.8 69.1 59.8 45.0 30.2 14.1 .001
Death due to breast cancer 8.2 7.8 7.8 9.1 11.1 15.3
Death due to other cause 14.1 19.5 27.5 40.7 53.9 67.4
Death due to unknown cause 2.9 3.6 4.9 5.3 4.8 3.3
Among women who died 1,873 4,256 5,130 4,902 3,287 1,747
Deaths due to breast cancer 32.4 25.3 19.4 16.5 15.9 17.8 .001
NOTE. Mantel-Haenszel test of trend was used for analyses.
Breast Cancer Among the Oldest Old
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Women with a CCI of 2 were more likely to receive mastectomy
(OR, 1.3; 95% CI, 1.3 to 1.4) or BCS alone (OR, 1.6; 95% CI, 1.5 to 1.8)
than BCS RT. The effect of age was stronger than the effect of
comorbidity on receipt of treatment. Among the subset of women
with a CCI of 0, 25.8% of women age 80 years received BCS alone or
no surgery compared with 6.0% of women age 65 to 79 years. No
significant interactions were observed between age and comorbidity
on types of treatment received.
Survival
Overall, median follow-up time was 5.6 years (interquartile
range, 3.3 to 8.7). Few women with stage I (4.5%) or stage II (16.1%)
disease died of breast cancer. Among women who died, the propor-
tion who died of breast cancer relative to other causes declined with
advancing age (Table 1). However, the risk of dying from breast cancer
increased significantly with age for women age 80 years compared
with younger women (Table 2). The risk of dying from other causes
was greater than the risk of dying from breast cancer at all ages
and stages.
Women treated with mastectomy, BCS alone, or no surgery
experienced worse breast cancer survival than those treated with BCS
RT (Appendix Table A1). However, for women treated with either
mastectomy or BCS alone, the risk of dying from breast cancer was
similar to the risk of dying from other causes. Women who received no
surgery had a substantially increased risk of dying from breast cancer
compared with those treated with BCS RT, and this risk exceeded
their risk of dying from other causes. However, few women did not
receive surgery. No significant interactions were observed between age
and treatment on breast cancer mortality; however, interactions be-
tween age (67 to 79 v 80 years) and types of treatment were signifi-
cant for non-breast cancer mortality.
Among women with ER-negative, lymph node–positive breast
tumors, we found that chemotherapy reduced breast cancer mortality
(adjusted hazard ratio [aHR], 0.8; range, 0.6 to 0.96). Since the inter-
action of age and chemotherapy was significant (P .03), we per-
formed subgroup analyses. Chemotherapy was associated with a
significant reduction in mortality for women age 67 to 79 years (aHR,
0.6; range, 0.5 to 0.8) and an increased risk of mortality for women
age 80 years (aHR, 1.5; range, 0.9 to 2.3) that did not achieve
statistical significance. Chemotherapy was associated with improved
non-breast cancer survival among all women (aHR, 0.6; range, 0.4
to 0.8).
Sensitivity Analyses
In analyses of women with known AJCC stage, known histologic
diagnosis, and no history of cancer, the impact of age, comorbidity,
and treatment on survival were similar (data not shown). Overall, our
results for the associations between treatment and survival outcomes
were also similar using propensity score methods (Table 3).
DISCUSSION
Breast cancer characteristics (eg, tumor grade, histology, hormone
receptivity) appear to be similar between women age 80 years
and younger women. However, women age 80 years receive less
aggressive treatment than younger women. Greater comorbidity
likely accounts for some of the observed difference; however,
Percent
Age (years)
100
80
60
40
20
90+
(n = 885)
85-89
(n = 2,449)
80-84
(n = 5,041)
75-79
(n = 7,561)
Mastectomy
BCS + XRT
BCS alone
No initial surgery
70-74
(n = 8,454)
67-69
(n = 4,507)
Fig 1. Initial treatment for stage I breast cancer by age at diagnosis. Receipt of
treatment differed by age at diagnosis for each stage using the Mantel-Haenszel
test of trend (P .001). BCS, breast-conserving surgery; XRT, radiation therapy.
Percent
Age (years)
100
80
60
40
20
90+
(n = 987)
85-89
(n = 1,795)
80-84
(n = 2,978)
75-79
(n = 4,105)
Mastectomy
BCS + XRT
BCS alone
No initial surgery
70-74
(n = 4,310)
67-69
(n = 2,407)
Fig 2. Initial treatment for stage II breast cancer by age at diagnosis. Receipt of
treatment differed by age at diagnosis for each stage using the Mantel-Haenszel
test of trend (P .001). BCS, breast-conserving surgery; XRT, radiation therapy.
Percent
Age (years)
100
80
60
40
20
85+
(n = 139)
80-84
(n = 254)
75-79
(n = 348)
Chemotherapy
70-74
(n = 453)
67-69
(n = 262)
Fig 3. Receipt of chemotherapy among women with estrogen receptor–
negative, lymph node–positive, stage I/II breast cancer.
Schonberg et al
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© 2010 by American Society of Clinical Oncology
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OURNAL OF CLINICAL ONCOLOGY
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among women with a Charlson score of 0, 26% of those age 80
years did not receive standard treatments (mastectomy or BCS
RT) for early-stage breast cancer compared with only 6% of
younger women. We also found that the risk of dying from breast
cancer increases significantly after age 80. Our findings suggest that
we may be able to identify a subgroup of women age 80 years
who may benefit from more aggressive work-up and treatment of
their early-stage breast cancer. Conversely, we may also be able to
Table 2. HR of Death Due to Breast Cancer and Other Causes by Age at Diagnosis and Stage
Characteristic
Known AJCC 3rd Edition Stage Imputed Stage
HR of Death Due to Breast Cancer Range HR of Death Due to Other Causes Range
Stage I
Age group, years
67-69 Reference Reference
70-74 1.0 0.9-1.2 1.4 1.3-1.6
75-79 1.1 0.9-1.3 2.2 2.0-2.3
80-84 1.4 1.2-1.7 3.3 3.0-3.5
85-89 1.7 1.3-2.1 4.8 4.3-5.2
90 2.6 2.0-3.4 7.2 6.5-8.1
Charlson comorbidity index
0 Reference Reference
1 1.2 1.1-1.4 1.7 1.6-1.8
2 1.7 1.5-1.9 2.7 2.6-2.8
Stage II
Age group, years
67-69 Reference Reference
70-74 1.0 0.9-1.2 1.3 1.2-1.4
75-79 1.1 0.99-1.3 1.9 1.8-2.2
80-84 1.2 1.1-1.4 3.0 2.7-3.3
85-89 1.5 1.3-1.7 4.1 3.7-4.6
90 1.8 1.5-2.2 5.9 5.2-6.7
Charlson comorbidity index
0 Reference Reference
1 1.1 1.0-1.3 1.7 1.6-1.8
2 1.3 1.2-1.4 2.6 2.5-2.8
NOTE. Each model was adjusted for tumor characteristics (grade, hormone receptivity, tumor size, histology, lymph node status none examined, none positive;
for stage II: one to three positive lymph nodes/unknown number of positive lymph nodes, four or more positive lymph nodes) and sociodemographics (age at
diagnosis, marital status, race/ethnicity, educational attainment of census tract/ZIP code, median household income of census tract/income, metropolitan v
nonmetropolitan status of residence, comorbidities Charlson comorbidity index, year of diagnosis, tumor registry, and breast cancer treatments).
Abbreviations: HR, hazard ratio; AJCC, American Joint Committee on Cancer.
Table 3. HR for Different Breast Cancer Treatments on Breast Cancer Death and Non-Breast Cancer Death
Characteristic
Known AJCC Stage Imputed Stage
Propensity Score Methods
(known AJCC stage imputed stage)
HR of Death Due to
Breast Cancer Range
HR of Death Due to
Other Causes Range
HR of Death Due to
Breast Cancer Range
HR of Death Due to
Other Causes Range
Stage I
BCS RT Reference Reference Reference Reference
Mastectomy 1.3 1.2-1.5 1.3 1.2-1.4 1.3 1.1-1.5 1.2 1.2-1.3
BCS alone 1.4 1.2-1.7 1.5 1.4-1.6 1.5 1.2-1.8 1.5 1.4-1.7
No surgery 7.2 5.4-9.6 2.7 2.3-3.2 7.2 3.6-14.3 1.7 1.3-2.3
Stage II
BCS RT Reference Reference Reference Reference
Mastectomy 1.5 1.3-1.6 1.5 1.4-1.6 1.5 1.3-1.7 1.3 1.2-1.4
BCS alone 1.7 1.5-2.0 1.6 1.4-1.8 1.8 1.4-2.3 1.8 1.5-2.0
No Surgery 5.3 4.2-6.8 2.6 2.2-3.1 3.9 2.2-7.1 2.0 1.4-2.9
NOTE. Each model was adjusted for tumor characteristics (grade, hormone receptivity, tumor size, histology, lymph node status none examined, none
positive; for stage II: one to three positive lymph nodes/unknown number of positive lymph nodes, four or more positive lymph nodes) and
sociodemographics (age at diagnosis, marital status, race/ethnicity, educational attainment of census tract/ZIP code, median household income of census
tract/income, metropolitan versus nonmetropolitan status of residence, comorbidities Charlson comorbidity index, year of diagnosis, tumor registry, and
breast cancer treatments).
Abbreviations: HR, hazard ratio; BCS, breast-conserving surgery; RT, radiation therapy.
Breast Cancer Among the Oldest Old
www.jco.org © 2010 by American Society of Clinical Oncology 2043
Page 6
identify a population of older women on the basis of tumor char-
acteristics, comorbid diseases, and life expectancy who may not
need as aggressive treatment. The majority of older women with
early-stage disease died from other causes. Future studies are
needed to develop tools that can help clinicians appropriately
target breast cancer treatments to the oldest women most likely
to benefit.
Despite prevailing opinion that breast cancer tumor characteris-
tics are more favorable among older women than younger women, we
generally did not find clinically important differences by age at diag-
nosis for most tumor characteristics. However, the youngest women
in our study were older than most women included in other studies.
25
It is possible that tumors present with more favorable characteristics
with older age but beyond age 67 years, these differences are negligible.
Other studies have also failed to show increases in hormone receptor
positivity among women age 70 years and older.
14,26
Although we and
others
27
have found that the proportion of women with positive
lymph nodes increased with age, we also found that the proportion of
women who had their lymph nodes examined declined substantially
with age, which may reflect biased sampling. Clinicians may be choos-
ing to sample only lymph nodes of older women who they suspect will
be positive.
Regardless of age, we found that the majority of older women
undergo surgery for treatment of breast cancer. Among women
with stage I disease, BCS RT is the most common treatment for
women age 67 to 79 years. Mastectomy is the most common
treatment for women age 80 to 84 years, which may reflect physi-
cians’ attempts to treat older women effectively but without radi-
ation. After age 85, BCS alone is the most common treatment.
Among women with stage II disease, mastectomy is the most
common treatment for all women, regardless of age; however, BCS
alone becomes substantially more common after age 80. Some of
the oldest women may be undertreated, while others may be being
treated appropriately. Future work should focus on identifying
tumor and patient characteristics associated with an improved
response to aggressive therapy among the oldest women.
As for the impact of RT on older women’s breast cancer
survival, we found that older women treated with BCS RT had
the best breast cancer survival. However, these women also had the
best overall survival, suggesting that unmeasured factors related to
survival affected treatment decisions. Clinical trials show that RT
after BCS compared with BCS alone reduces breast cancer recur-
rence among older women with early-stage disease but does not
affect survival.
8,28,29
Since we found that breast cancer mortality
increases significantly after age 80 and these women are the least
likely to be treated aggressively, our findings suggest that some
older women in good health may benefit from more aggres-
sive treatment.
We found that treatment with chemotherapy was associated with
a survival benefit for women age 67 to 79 years with ER-negative,
lymph node–positive disease, results similar to those in other stud-
ies.
6,7
However, chemotherapy tended to be associated with worse
breast cancer survival among women age 80 years. Since few
women age 80 years received chemotherapy, our findings suggest
that chemotherapy is reserved for the oldest women with the worst
tumor characteristics.
This study has several important limitations. Since this is an
observational study, there is potential for selection bias and resid-
ual confounding by factors for which we do not have data, such as
performance status, social support, and treatment with hormonal
therapy. In post hoc sensitivity analyses, we examined the effect of
an unmeasured confounder such as hormonal therapy on our
estimated aHRs. Assuming that treatment with tamoxifen is more
common among women age 80 years than among younger
women
30
and that the survival benefit of tamoxifen ranges from
10% to 50% reduction in breast cancer mortality,
31
we found that
our aHRs would decrease by less than 10% if we were able to adjust
for tamoxifen use.
32,33
Completion of death certificate data could
also differ by age. However, studies have found that coding of
cancer on death certificates is accurate, particularly coding of
breast cancer death.
34,35
In addition, administrative data may un-
derestimate the prevalence of many chronic conditions. Moreover,
we needed to exclude women who had missing claims data, the
majority of whom had health maintenance organization coverage.
Health maintenance organizations tend to include younger and
healthier women, which may mean that our sample of women age
67 to 79 years may be older and in poorer health than the overall
population. However, this would bias our comparisons between
the oldest-old and younger-old toward the null. AJCC staging was
modified in 2003 such that women with four or more positive
lymph nodes are now classified as stage III. However, only 4.7% of
women in our sample had four or more positive nodes. Changes in
staging had no effect on women classified as stage I. Finally, al-
though socioeconomic status data were community level, studies
have demonstrated moderate associations between individual and
aggregate socioeconomic characteristics.
20
In summary, breast cancer characteristics are similar among
women age 80 years and younger women. However, women
age 80 years receive less aggressive treatment and are more
likely to die from breast cancer. Future studies should focus on
identifying tumor and patient characteristics that can be used to
help target breast cancer treatments to the oldest women most
likely to benefit.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
The author(s) indicated no potential conflicts of interest.
AUTHOR CONTRIBUTIONS
Conception and design: Mara A. Schonberg, Edward R. Marcantonio,
Rebecca A. Silliman, Ellen P. McCarthy
Financial support: Mara A. Schonberg
Administrative support: Mara A. Schonberg
Collection and assembly of data: Mara A. Schonberg, Donglin Li
Data analysis and interpretation: Mara A. Schonberg, Edward R.
Marcantonio, Donglin Li, Rebecca A. Silliman, Long Ngo,
Ellen P. McCarthy
Manuscript writing: Mara A. Schonberg, Edward R. Marcantonio,
Donglin Li, Rebecca A. Silliman, Long Ngo, Ellen P. McCarthy
Final approval of manuscript: Mara A. Schonberg, Edward R.
Marcantonio, Donglin Li, Rebecca A. Silliman, Long Ngo,
Ellen P. McCarthy
Schonberg et al
2044 © 2010 by American Society of Clinical Oncology
J
OURNAL OF CLINICAL ONCOLOGY
Page 7
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    • "Despite this increase, older survivors are understudied relative to pediatric survivors. Furthermore, in comparison with their younger counterparts, older adults with cancer experience several inadequacies in their cancer treatment and care, such as receiving less aggressive treatments (Bastiaannet et al., 2010; Schonberg et al., 2014; Schonberg et al., 2010). Despite known differences in treatment, few studies have examined how older, middle-aged, and younger adults with cancer choose their treatment (Elkin, Kim, Casper, Kissane, & Schrag, 2007; Lifford et al., 2015; Pinquart & Duberstein, 2004), and how the decision-making (DM) process differs by age (Puts et al., 2015; Shelton et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: The aim of this study was to examine the decision-making (DM) styles of younger (18-39 years), middle-aged (40-59 years), and older (≥60 years) cancer survivors, the type and role of social support, and patient satisfaction with cancer treatment DM. Method: Adult cancer survivors (N = 604) were surveyed using Qualtrics online software. Results: Older adults reported significantly lower influence of support on DM than younger adults. The most common DM style for the age groups was collaborative DM with their doctors. Younger age was a significant predictor of independent (p < .05), collaborative with family (p < .001), delegated to doctor (p < .01), delegated to family (p < .001), and demanding (p < .001) DM styles. Discussion: Despite having lower received social support in cancer treatment DM, older adults were more satisfied with their DM than younger and middle-aged adults. Health care workers should be aware of different DM styles and influence of social networks to help facilitate optimal patient DM and satisfaction.
    Full-text · Article · Feb 2016
    • "The influence of age on BC prognosis is controversial, and the literature contains many conflicting reports. As a patient reaches old age, there is a progressive decrease in survival [31]. Surprisingly, the multivariate analysis of our study cohort did not find this correlation to be a predictor of survival. "
    Article · Jan 2016
    • "These biological features were not linked to favourable disease evolution, but this result must be interpreted cautiously in elderly patients. Undertreatment in older patients with breast cancer is known to have a strong negative effect on survival [36,525354. Furthermore, in our study, evolution criteria were: local relapse, metastatic relapse, or death. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Breast cancer biological characteristics change as age advances. Today, there is a lack of knowledge regarding age-specific molecular alterations that characterize breast tumours, notably in elderly patients. The vast majority of studies that aimed at exploring breast cancer in function of age are based on clinico-pathological data. Gene-expression signatures (GES), which in some ways capture biological information in a non-reductionist manner, represent powerful tools able to explore tumour heterogeneity. Methods Twenty-five GES were used for functional annotation of breast tumours in function of age: five for molecular subtyping, seven for immune response, three for metabolism, seven for critical pathways in cancer and three for prognosis. Affymetrix® genomics datasets were exclusively used to avoid cross-platform normalization issues. Available corresponding clinico-pathological data were also retrieved and analysed. Results Fifteen publicly available datasets were pooled for a total of 2378 breast cancer patients (whole cohort), out of whom 1413 were of Caucasian origin. Three age groups were defined: ≤ 40 years (AG1), > 40 to < 70 years (AG2) and ≥ 70 years (AG3). We confirmed that age influenced the incidence of molecular subtypes. We found a significant growing incidence of luminal B and a decreasing kinetics for basal-like in function of age. We showed that AG3 luminal B tumours were less aggressive than AG1 luminal B tumours based on different GES (iron metabolism, mitochondrial oxidative phosphorylation and reactive stroma), recurrence score prognostic GES and histological grade (SBR). Contrary to tumours of young patients, tumours of elderly patients concentrated favourable GES scores: high oestrogen receptor and mitochondrial oxidative phosphorylation, low proliferation, basal-like, glycolysis, chromosomal instability and iron metabolism, and low GES prognostic scores (van’t Veer 70-GES, genomic grade index and recurrence score). Conclusions Functional annotation of breast tumours by means of 25 GES demonstrated a decreasing aggressiveness of breast tumours in function of age. This strategy, which can be strengthened by increasing the number of representative GES to gain more insight into biological systems involved in this disease, provides a framework to develop rational therapeutic strategies in function of age.
    Full-text · Article · Dec 2015
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