My cancer mass is termed Stage 2b. This means it can be large as I had 14 cm and
it was not in the lymph nodes or organs, bones or brain.
|
breast cancer sub-type
|
Estimated Overall Survival
|
|
DCIS-ductal carcinoma in situ)
|
98% to 100%
|
|
Tubular breast carcinoma
|
95%
|
|
Infiltrating
lobular carcinoma
|
86%
|
|
Infiltrating ductal carcinoma
|
84%
|
|
Medullary breast carcinoma
|
78%
|
|
Mucinous breast carcinoma
|
75%
|
|
Inflammatory breast carcinoma
|
32% to 42%
|
Infiltrating/invasive lobular breast carcinoma
I have lobular breast carcinoma
Breast
Cancer Among the Oldest Old: Tumor Characteristics, Treatment Choices, and
Survival
+ Author Affiliations
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.
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 Despite 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 controlled 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, Epidemiology and End
Results (SEER) -Medicare data set have examined the effectiveness of radiation
treatment and chemotherapy among older women with breast cancer.5–8 However, these studies consistently exclude women with
missing stage and those without 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
Although studies consistently show that
older women are undertreated for breast cancer, the impact of undertreatment on
breast cancer survival among older women remains controversial. Gadjos et al3 found that rates of recurrence were not increased when
undertreated women (older than 70 years) were compared with conventionally
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 Connecticut, 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 Medicare 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 diagnosis (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 tumor
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 κ statistic. Because of the observed excellent agreement (the
two-sided κ 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 progesterone receptivity. Variable definitions can be found in
Appendix B (online 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 categorized 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
substituted 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 standard 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 sociodemographics, 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 treatments 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 confounding, 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 macro24 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
Average the survival
rate can be estimated at about 86%.
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).
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.
View
larger version:
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.
View
larger version:
Fig 3.
Receipt of chemotherapy among women with
estrogen receptor–negative, lymph node–positive, stage I/II breast cancer.
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. 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 proportion
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.
View this table:
Table 2.
HR of Death Due to Breast
Cancer and Other Causes by Age at Diagnosis and Stage
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
between age (67 to 79 v ≥ 80 years) and types of
treatment were significant 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
interaction of age and chemotherapy was significant (P = .03), we performed
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).
View this table:
Table 3.
HR for Different Breast
Cancer Treatments on Breast Cancer Death and Non-Breast Cancer Death
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, 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 identify a population of older women on the basis of
tumor characteristics, 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 characteristics are more favorable among older women than younger
women, we generally did not find clinically important differences by age at
diagnosis 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 others27 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 choosing 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 physicians' attempts to treat older women effectively
but without radiation. 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 recurrence 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 aggressive 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
studies.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 residual 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 women30 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
underestimate 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,
although 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
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