Breast implants following mastectomy in women with early-stage breast cancer: prevalence and impact on survival

Article (PDF Available)inBreast cancer research: BCR 7(2):R184-93 · February 2005with17 Reads
DOI: 10.1186/bcr974 · Source: PubMed
Abstract
Few studies have examined the effect of breast implants after mastectomy on long-term survival in breast cancer patients, despite growing public health concern over potential long-term adverse health effects. We analyzed data from the Surveillance, Epidemiology and End Results Breast Implant Surveillance Study conducted in San Francisco-Oakland, in Seattle-Puget Sound, and in Iowa. This population-based, retrospective cohort included women younger than 65 years when diagnosed with early or unstaged first primary breast cancer between 1983 and 1989, treated with mastectomy. The women were followed for a median of 12.4 years (n = 4968). Breast implant usage was validated by medical record review. Cox proportional hazards models were used to estimate hazard rate ratios for survival time until death due to breast cancer or other causes for women with and without breast implants, adjusted for relevant patient and tumor characteristics. Twenty percent of cases received postmastectomy breast implants, with silicone gel-filled implants comprising the most common type. Patients with implants were younger and more likely to have in situ disease than patients not receiving implants. Risks of breast cancer mortality (hazard ratio, 0.54; 95% confidence interval, 0.43-0.67) and nonbreast cancer mortality (hazard ratio, 0.59; 95% confidence interval, 0.41-0.85) were lower in patients with implants than in those patients without implants, following adjustment for age and year of diagnosis, race/ethnicity, stage, tumor grade, histology, and radiation therapy. Implant type did not appear to influence long-term survival. In a large, population-representative sample, breast implants following mastectomy do not appear to confer any survival disadvantage following early-stage breast cancer in women younger than 65 years old.

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Available online http://breast-cancer-research.com/content/7/2/R184
R184
Vol 7 No 2
Research article
Breast implants following mastectomy in women with early-stage
breast cancer: prevalence and impact on survival
Gem M Le1, Cynthia D O'Malley1, Sally L Glaser1, Charles F Lynch2, Janet L Stanford3,
Theresa HM Keegan1 and DeeWWest
1
1Northern California Cancer Center, Fremont, California, USA
2Iowa Cancer Registry, University of Iowa, Iowa City, Iowa, USA
3Fred Hutchison Cancer Research Center, Division of Public Health Sciences, Seattle, Washington, USA
Corresponding author: Gem M Le, gle@nccc.org
Received: 16 Jul 2004 Revisions requested: 10 Sep 2004 Revisions received: 25 Oct 2004 Accepted: 16 Nov 2004 Published: 23 Dec 2004
Breast Cancer Res 2005, 7:R184-R193 (DOI 10.1186/bcr974)http://breast-cancer-research.com/content/7/2/R184
© 2004 Le et al., licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/
2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is cited.
Abstract
Background Few studies have examined the effect of breast
implants after mastectomy on long-term survival in breast cancer
patients, despite growing public health concern over potential
long-term adverse health effects.
Methods We analyzed data from the Surveillance,
Epidemiology and End Results Breast Implant Surveillance
Study conducted in San Francisco–Oakland, in Seattle–Puget
Sound, and in Iowa. This population-based, retrospective cohort
included women younger than 65 years when diagnosed with
early or unstaged first primary breast cancer between 1983 and
1989, treated with mastectomy. The women were followed for a
median of 12.4 years (n = 4968). Breast implant usage was
validated by medical record review. Cox proportional hazards
models were used to estimate hazard rate ratios for survival time
until death due to breast cancer or other causes for women with
and without breast implants, adjusted for relevant patient and
tumor characteristics.
Results Twenty percent of cases received postmastectomy
breast implants, with silicone gel-filled implants comprising the
most common type. Patients with implants were younger and
more likely to have in situ disease than patients not receiving
implants. Risks of breast cancer mortality (hazard ratio, 0.54;
95% confidence interval, 0.43–0.67) and nonbreast cancer
mortality (hazard ratio, 0.59; 95% confidence interval, 0.41–
0.85) were lower in patients with implants than in those patients
without implants, following adjustment for age and year of
diagnosis, race/ethnicity, stage, tumor grade, histology, and
radiation therapy. Implant type did not appear to influence long-
term survival.
Conclusions In a large, population-representative sample,
breast implants following mastectomy do not appear to confer
any survival disadvantage following early-stage breast cancer in
women younger than 65 years old.
Keywords: breast implants, epidemiology, mastectomy, Surveillance, Epidemiology, and End Results, survival
Introduction
Over the past 30 years, an estimated 1.5–2 million women
have received breast implants in the United States [1].
Starting in the 1980s, widespread public health concern
arose regarding their potential adverse health effects [2].
Numerous epidemiologic investigations have focused on
systemic complications, particularly cancer and connective
tissue disease, but have found no significantly increased
short-term risk for these diseases [3,4].
Approximately 20% of breast implants are used for recon-
struction in breast cancer patients following mastectomy
[1]. In this population, however, the use of breast implants,
while increasing, has not been well documented [5]. Fur-
thermore, little research has addressed long-term survival,
although the few studies conducted suggest that use of
implants for breast reconstruction does not impact patient
survival [6-9]. However, these studies were limited by com-
prising clinic-based samples not necessarily representative
of all patients, by small sample sizes, by lack of information
on type of implant, and by short durations of follow-up.
In 1993, the Surveillance, Epidemiology, and End Results
(SEER) program of the National Cancer Institute
SEER = Surveillance, Epidemiology, and End Results; SES = socioeconomic status.
Breast Cancer Research Vol 7 No 2 Le et al.
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implemented the Breast Implant Surveillance Study to doc-
ument and validate postmastectomy breast implant usage
in a population-based series of young, early-stage breast
cancer cases. Since the SEER program also monitors
patient vital status for life, survival up to 17 years exists in
the study cohort. The purpose of the current analysis was
to describe the use of breast implants and to examine the
impact of breast implants on survival after breast cancer in
this cohort.
Methods
Breast Implant Surveillance Study
The Breast Implant Surveillance Study was conducted dur-
ing the period 1993–1994 in the United States. Patients
were identified through the population-based SEER cancer
registries in San Francisco–Oakland, CA, in Seattle–Puget
Sound, WA, and in the state of Iowa. Eligible patients
included the 5862 females diagnosed younger than age 65
with early-stage or unstaged first primary breast cancer in
1983, 1985, 1987, or 1989 and treated with mastectomy
during their first course of therapy.
Participation involved completing a standardized question-
naire inquiring about implant status (right breast only, left
breast only, both breasts, no implant, or unknown) and
implant type (silicone gel, saline, double lumen [consisting
of silicone gel and saline], other, and unknown type), and
providing signed consent for release of medical records for
validation of implant usage and implant type. Patients in the
Seattle–Puget Sound region and the state of Iowa were
mailed a self-administered questionnaire, and nonrespond-
ents were contacted for a telephone interview. Women
from the San Francisco–Oakland region were administered
questionnaires by telephone.
Next-of-kin were asked about the deceased patient's
implant status and for consent for medical record review.
For women reporting breast implants, a medical record
review of breast implant usage (including the date and type
of implant received, and removal and replacement status)
was conducted by trained abstractors for women who
reported having a breast implant. Patient and tumor charac-
teristics at diagnosis, including age, race/ethnicity, year,
stage, histology, grade, radiation treatment, vital status, and
cause of death, were obtained from the SEER database.
Although socioeconomic status (SES) is not routinely col-
lected by SEER, we were able to assign census block
group level measures of SES to a subset of subjects (1989
San Francisco Bay Area patients). Using data from the
1990 US Census, we examined the impact of living in cen-
sus block groups characterized by low education, by pov-
erty, and by occupation (median income, < 20% below
poverty versus 20% below poverty; education, no high
school diploma versus high school graduate; and occupa-
tion, blue collar versus nonblue collar [10]).
Patients who reported a breast implant were classified as
having a particular type of implant if they had a unilateral
implant, or if they had bilateral implants of the same type.
Nineteen women with bilateral implants and discordant
information about implant type were excluded from analy-
ses stratified by the type of implant. An additional 133
women reporting implants but lacking implant information
were excluded from all analyses requiring detailed implant
information. The vital status (obtained annually through
patient contact, death records, motor vehicle departments,
voters' registration records, and Social Security files) was
determined from the December 1999 SEER Public Use
Tape. The outcome variables were death due to breast can-
cer and death due to nonbreast cancer causes, as routinely
ascertained by SEER and as defined by the International
Classification of Disease, Ninth Revision, codes 174.0–
174.9 for deaths occurring between 1983 through 1998,
and by the International Classification of Disease, 10th
Revision, code C509 for deaths occurring in 1999. Survival
time was calculated from the date of diagnosis to the earli-
est date: death, last known to be alive, or 31 December
1999 (study cutoff date).
Statistical analysis
For descriptive analyses, women with breast implants were
compared with those without implants on characteristics at
diagnosis (SEER region of residence, age, year, race/eth-
nicity, marital status, stage, grade, and histology), using chi-
square tests and Fisher's exact test to assess differences.
Two-sided P < 0.05 was considered statistically
significant.
Of the 5862 patients eligible for the study, 4968 (84.7% of
those eligible) patients participated in the study. After
restricting the sample to women with primary invasive
breast cancer and known survival time, a final sample size
of 4385 patients were used for all survival analyses. Sur-
vival estimates were computed using the Kaplan–Meier
method, and differences in survival were compared using
the two-sided log-rank test. To adjust for patient and tumor
characteristics, the risks of nonbreast cancer mortality and
death due to breast cancer were modeled using Cox pro-
portional hazards regression after censoring deaths from
other or unknown causes. The assumption of proportional-
ity was tested and met for all covariates used in the Cox
analysis. All analyses were performed using SAS Version
8.02 (SAS Institute, Inc., Cary, NC, USA).
Results
Study population
Eighty-five percent of study-eligible women completed the
interview. Responders were slightly older compared with
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Table 1
Characteristics of mastectomy-treated breast cancer patients in the Surveillance, Epidemiology, and End Results (SEER) Breast
Implant Surveillance Study, 1983–1989
Characteristic All eligible patients (n = 5862) Study responders only (n = 4968)
Nonresponders (n = 894) Responders (n = 4968) P value Women with breast implants
(n = 1018) Women without breast
implants (n = 3950) P value
n%n%n%n%
SEER region
San Francisco–Oakland 468 52.4 1853 37.3 0.0001 416 40.9 1437 36.4 0.0001
Seattle–Puget Sound 190 21.3 1663 33.5 374 36.7 1078 27.3
Iowa 236 26.4 1452 29.2 228 22.4 1435 36.3
Year of diagnosis
1983 246 27.5 1102 22.2 0.0001 176 17.3 926 23.4 0.0003
1985 241 27.0 1152 23.2 244 24.0 908 23.0
1987 230 25.7 1405 28.3 319 31.3 1086 27.5
1989 177 19.8 1309 26.3 279 27.4 1030 26.1
Age at diagnosis
< 35 years 59 6.6 175 3.5 0.0001 88 8.6 87 2.2 0.0001
35–44 years 231 25.8 919 18.4 334 32.8 585 14.8
45–54 years 256 28.6 1545 31.1 370 36.4 1175 29.8
55–64 years 348 38.9 2329 46.9 226 22.2 2103 53.2
Mean age at diagnosis (years) 49.9 - 52.1 - 0.0001 46.7 - 53.4 - 0.0001
Race/ethnicity
Non-Hispanic White 670 74.9 4444 89.5 0.0001 959 94.2 3485 88.2 0.0001
Non-Hispanic Black 78 8.7 150 3.0 13 1.3 137 3.5
Hispanic 38 4.3 131 2.6 20 2.0 111 2.8
Asian/Pacific Islander 86 9.6 179 3.6 16 1.6 163 4.1
Other/unknown 22 2.5 64 1.3 10 1.0 54 1.4
Stage at diagnosis
In situ 78 8.7 567 11.4 0.04 199 19.6 368 9.3 0.0001
Localized 562 62.9 3141 63.2 601 59.0 2540 64.3
Regional 241 27.0 1209 24.3 211 20.7 998 25.3
Unstaged 13 1.5 51 1.0 7 0.7 44 1.1
Histology
Infiltrating ductal 687 76.9 3638 73.2 0.04 695 68.3 2943 74.5 0.0001
Lobular 44 4.9 364 7.3 106 10.4 258 6.5
Infiltrating ductal and lobular 35 3.9 195 3.9 54 5.3 141 3.6
Not otherwise specified/
other 128 14.3 771 15.5 163 16.0 608 15.4
Grade
Well differentiated 17 1.9 150 3.0 0.02 29 2.9 121 3.1 0.91
Moderately differentiated 128 14.3 712 14.3 137 13.5 575 14.6
Poorly differentiated 144 16.1 824 6.6 169 16.6 655 16.6
Undifferentiated 17 1.9 185 3.7 39 3.8 146 3.7
Unknown grade 588 65.8 3097 62.3 644 63.3 2453 62.1
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nonresponders. They also were more often non-Hispanic
white, were diagnosed with in situ cancers, were less likely
to have more than one primary tumor and were more likely
to have lived until the end of the study period (Table 1).
Among the responders, 20% received a breast implant
(Table 1). Their mean age at diagnosis was 47 years, and
they were younger, on average, than women without
implants. Somewhat higher proportions of women with
implants were of non-Hispanic white race/ethnicity, resided
in the San Francisco–Oakland region, were diagnosed in
the late 1980s, and had tumors of lobular histology than
women without implants. The percentage of women with in
situ breast cancer was twice as high in women with breast
implants as in nonimplanted women. In addition, women
with implants were less likely to receive radiation therapy or
to be diagnosed with more than one primary tumor.
Implant characteristics and usage
Implant information was obtained for 866 women; these
women were slightly older and more likely to be living than
women with unknown implant information. Among the
1143 breast implants received (Table 2), the most common
types were silicone gel and double lumen. The majority of
women (67%) received a unilateral implant a median of 9.6
months after breast cancer diagnosis. Approximately one-
third of the women had an implant removed; the majority of
these women chose to have the implant replaced. Saline-
filled implants were removed for 48% of women, although
saline-filled tissue expanders (temporary implants) may be
incorrectly included in this category. Fifty-four percent of
women with 'other' implants had them removed, and 49%
had them replaced.
Survival
At the end of the follow-up period, 231 (5.3%) patients did
not have complete follow-up. Twenty-eight percent of all
patients died, with nearly two-thirds of these deaths due to
breast cancer (Table 3). Women with implants had a similar
distribution of causes of death to those without implants
(Table 3), except for a significantly larger proportion of
deaths due to suicide – although this was based on a small
number of deaths (0.4% versus 0.03% of all patients,
respectively; P = 0.02). Among the 4385 patients with
invasive breast cancer and known survival time, the 817
(19%) receiving a breast implant experienced better sur-
vival than women without implants, after adjustment for age
at diagnosis (Fig. 1).
The multivariate Cox proportional hazards model showed
that implant status was a significant factor associated with
improved survival for deaths due to breast cancer and for
nonbreast cancer mortality (Table 4). Risk of breast cancer
death in women with implants was approximately one-half
of that for women without implants, after adjustment for
multiple clinical and sociodemographic factors. Age at
diagnosis, stage, grade, histology, and radiation therapy
were significant predictors of breast cancer death in this
cohort, as they were for women without implants. With the
exception of age, results were similar when modeled for
nonbreast cancer mortality, although hazard rate ratios for
women with implants were slightly higher overall. Among
women with implants, the type of breast implant did not sig-
nificantly impact survival, although women receiving saline
implants had marginally lower risks than women receiving
silicone gel implants.
For the subsample of 384 San Francisco Bay Area study
subjects for whom we were able to assign census-level
SES indicators, risk of death among women with breast
implants compared with that among women without
implants continued to be reduced (hazard ratio, 0.50; 95%
confidence interval, 0.20–1.25) after adjustment for cen-
sus block-group level SES variables.
Number of primary tumors
One primary only 771 86.2 4001 80.5 0.0001 867 85.2 3134 79.3 0.0001
Two or more primaries 123 13.8 967 19.5 151 14.8 816 20.7
Radiation therapy during first
course of treatment
No 814 91.1 4626 93.1 0.03 969 95.2 3657 92.6 0.01
Yes 80 9.0 333 6.7 48 4.7 285 7.2
Unknown 0 0 9 0.2 1 0.1 8 0.2
Vital statusa
Alive 538 60.2 3696 74.4 0.0001 867 85.2 2828 71.6 0.0001
Dead 356 39.8 1272 25.6 151 14.8 1122 28.4
aFinal date of follow-up, December 1999.
Table 1 (Continued)
Characteristics of mastectomy-treated breast cancer patients in the Surveillance, Epidemiology, and End Results (SEER) Breast
Implant Surveillance Study, 1983–1989
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Discussion
In this large population-based study of breast cancer
patients treated with mastectomy, risks of breast cancer
death and nonbreast cancer mortality were lower in women
with implants than in women without implants, after adjust-
ment for potential confounders. Postmastectomy breast
implants were used by one-fifth of patients who were
slightly younger at diagnosis and were more likely to be of
white race/ethnicity and to have in situ disease than
women without implants. The silicone gel-filled implant was
the most common type of implant received.
Although breast reconstruction has been shown to provide
psychosocial benefits to breast cancer survivors [11-13],
concerns have been raised that breast implants may
increase the risk of local complications and systemic
diseases, including certain cancers and autoimmune dis-
eases [2,3,14,15]. Breast implants have been suggested
to interfere with mammography, thereby facilitating delayed
detection of breast tumors, and, consequently, decreased
survival [16]. Despite recent Institute of Medicine recom-
mendations to continue monitoring women with breast
implants and to evaluate the potential long-term health
effects [1], few research studies have addressed long-term
health outcomes in this group. Moreover, these studies
were often conducted on small, nonrepresentative samples
without detailed information on implant type and history of
use.
Georgiade and colleagues found that the survival time for
101 women undergoing breast reconstruction with breast
implants was nonsignificantly better than that for 377
women without reconstruction, after adjustment for tumor
grade, histology, lymph node involvement, and age at diag-
nosis, and after a median of 3 years of follow-up [6]. With
a median of 13 years of follow-up, Petit and colleagues
found that the risk of breast cancer death was marginally
lower in 146 women who underwent breast reconstruction
with silicone gel-filled implants than in a matched group
without implants (relative risk, 0.6; 95% confidence inter-
val, 0.3–1.1) [7]. Vandeweyer and colleagues compared
49 women who received saline-filled breast implants fol-
lowing mastectomy with a matched group of women who
did not. They found no difference in the number of breast
cancer deaths between the two groups [8]. In a matched
analysis of 176 women with a mean of almost 6 years of fol-
low-up, Park and colleagues found that women with breast
implants after mastectomy had approximately a 70%
reduced risk of death compared with women without
implants (relative risk, 0.33; 95% confidence interval,
0.11–0.92) [9].
Our finding of better survival in women with breast implants
is consistent with most of this research [6-8]. However, our
study has the substantial advantages of being population-
based, being large, having a long follow-up (median, 12.4
years), and including information on implant type and the
implant removal and replacement. It is thus well suited to
address public health concerns regarding the long-term
survival and use of breast implants in women with early-
stage, mastectomy-treated breast cancer. Such concerns
have recently been re-evaluated in conjunction with the
Food and Drug Administration hearings regarding the
safety of silicone gel breast implants and their availability for
the general market [17,18].
One explanation for our finding of reduced mortality in
patients with breast implants may relate to self-selection
rather than to a causal role of implants. Although most
women who receive mastectomy are eligible to receive
breast implants as part of breast reconstruction, surgeons
may not recommend this surgery to women with health con-
ditions such as obesity or a recent history of smoking that
may contribute to postoperative complications, and may
thus impact on survival [19,20]. In our data, the possibility
of self-selection based on smoking is supported by the
Table 2
Characteristics of breast implants in mastectomy-treated breast cancer patients in the Surveillance, Epidemiology, and End Results
Breast Implant Surveillance Study, 1983–1989 (n = 866)a
Silicone gel (n = 333) Saline (n = 149) Double lumen (n = 314) Other (n = 33) Unknown (n = 37) P value
n%n%n%n%n%
Prevalence of type 38.4 17.2 36.3 3.8 4.3
Implant removal status
No known removal 244 73.3 77 51.7 216 64.9 15 45.5 25 67.6 0.0001
Removed 89 26.7 72 48.3 98 31.2 18 54.5 12 32.4
Implant replacement status
No known replacement 262 78.7 87 58.4 237 75.4 17 51.5 26 70.3 0.0001
Replaced 71 21.3 62 41.6 77 24.5 16 48.5 11 29.7
aExcludes 133 patients with missing implant information and 19 patients with bilateral implants of disordant types
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higher proportions of deaths from respiratory cancers and
chronic obstructive pulmonary diseases in women without
breast implants (Table 3). Further investigation is warranted
for lifestyle factors (e.g. smoking, diet) and for comorbidi-
ties that may account for the survival advantage seen in
women with breast implants.
In the present study, women with breast implants had a sig-
nificant excess proportion of deaths due to suicide com-
pared with women without implants. This finding, albeit
based on small numbers, is consistent with observations
from studies conducted in cosmetic breast implant patients
[21,22] and suggests psychiatric consultation should also
be considered for breast cancer patients seeking recon-
structive surgery with breast implants. In any case, future
studies with larger sample sizes are needed to confirm this
finding in the breast reconstruction population.
An important bias of common concern in retrospective
cohort studies is loss to follow-up. A total 231 (5.3%) of the
4385 patients included in the survival analysis did not have
complete follow-up at the end of the study period. How-
ever, because of the relatively small percentage of patients
lost to follow-up, we know that bias due to loss to follow-up
has little impact on our survival findings since we found no
substantial change in hazards ratios when we assumed the
worst-case scenario that all patients lost to follow-up had
all died or assumed that all patients lost to follow-up all lived
until the end of the study period.
Furthermore, although our response rate was relatively
high, differences between nonresponders and responders
on several patient and tumor characteristics could have
biased our findings. Although we were able to adjust for
reported patient and tumor characteristics in our multivari-
ate analyses, 356 women (nearly 40% of study-eligible
patients) who did not participate in the study were
deceased. In the unlikely event that all 356 deceased
women had received breast implants, it is possible that the
exclusion of these cases from our analysis could bias our
results towards and beyond the null, and thereby overesti-
mate the protective effects.
Although our survival analyses were adjusted for various
demographic and clinical characteristics, our finding of bet-
ter survival in women with breast implants could reflect
uncontrolled confounding by social class, medical care,
and psychological factors related to implant usage and
survival. Among breast cancer patients treated with mas-
tectomy, those choosing to have breast reconstruction
have been shown to differ from women without breast
reconstruction on SES, which may be an important factor
affecting survival [23,24]. In a convenience sample of more
than 200,000 breast cancer patients undergoing mastec-
tomy between 1985 and 1995, Morrow and colleagues
found that patients with a family income of $40,000 or
more were twice as likely as patients with a family income
of less than $40,000 to receive postmastectomy breast
reconstruction [25]. Higher income may be a predictor of
better survival after breast cancer, as women with higher
incomes may have better access to cancer care and treat-
ment. In the present study, SES did not alter the effect of
implants on survival in the subset of women for whom SES
measures were available. Differences in these area-level
measures of SES are thus not likely to contribute substan-
tially to the survival differences between breast cancer
patients with and without implants in this study.
Additional unmeasured confounders related to the
increased medical care of women with breast implants
could explain the protective association of breast implants
with cancer survival. Because women with breast implants
may be more closely followed in their medical care, they
may have recurrences diagnosed and treated earlier; thus
they may experience better survival than women without
implants. Although our study lacked information on breast
cancer recurrence, we were able to examine the impact of
subsequently diagnosed primary breast tumors. We
observed that the proportion of women with two or more
primary breast tumors was lower in women with breast
implants than in women without (15% and 21%,
respectively).
To address the possibility that a higher incidence of subse-
quently diagnosed primary breast tumors impacted survival
in women without breast implants, we limited survival anal-
yses to women with only one primary tumor (n = 3535) and
found a consistently reduced risk of breast cancer death
associated with breast implant usage (hazard ratio, 0.54;
95% confidence interval, 0.42–0.68), after adjusting for
similar prognostic factors. Our findings also are consistent
Figure 1
Age-adjusted breast cancer survival curve by breast implant status, 1983–1989Age-adjusted breast cancer survival curve by breast implant status,
1983–1989.
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with results from studies showing a reduced risk of death
in augmentation mammoplasty patients with at least 10
years of follow-up compared with the general population
[26-29]. Furthermore, psychological factors underlying a
woman's decision to obtain breast implants [30,31], includ-
ing body image concerns and self-esteem, may play a role
in lifestyle behaviors relevant to survival, although the extent
to which they directly impact survival is unclear.
Several biological mechanisms have been proposed to
explain how breast implants may influence survival out-
comes [16,26,32,33]. Breast implants may stimulate a
local immune response in which cancer cells are more likely
to be destroyed [34]. Breast implants may compress breast
tissue, reducing the flow of blood and thereby slowing the
rate of cell or tumor growth. Breast implants may decrease
the temperature of the breast by separating the breast tis-
Table 3
Distribution of living and deceased patients by breast implant status in the Surveillance, Epidemiology, and End Results Breast
Implant Surveillance Study, 1983–1989 (n = 4385)
Women with breast implants
(n = 817) Women without breast implants
(n = 3568) Total (n = 4385) P valuea
n%n%n%
Alive 676 82.3 2498 70.0 3174 72.4 < 0.0001
Deceased
All malignant cancers
Digestive system 2 0.2 32 0.9 34 0.8 0.08
Respiratory 3 0.4 51 1.4 54 1.2 0.01
Breast 101 12.4 703 19.7 804 18.3 < 0.0001
Female genital 4 0.5 20 0.6 24 0.5 0.80
Kidney - - 2 0.1 2 0.2 -
Brain - - 7 0.2 7 0.2 -
Melanoma 1 0.1 2 0.1 3 0.1 0.46
Multiple myeloma - - 3 0.1 3 0.1 -
Non-Hodgkin's lymphoma - - 3 0.1 3 0.1 -
Leukemia 2 0.2 2 0.1 4 0.1 0.16
Diabetes mellitus 2 0.2 13 0.4 15 0.3 0.60
Circulatory system
Heart disease 4 0.5 65 1.8 69 1.6 0.01
Cerebrovascular disease 2 0.2 14 0.4 16 0.4 0.75
Atherosclerosis - - 3 0.1 3 0.1 -
Respiratory disease
Pneumonia/influenza 1 0.1 10 0.3 11 0.3 -
Chronic obstructive pulmonary disease 2 0.2 23 0.6 25 0.6 0.21
Digestive system disease
Stomach/duodenal ulcers - - 3 0.1 3 0.1 -
Chronic liver disease 1 0.1 7 0.2 8 0.2 -
Nephritis - - 7 0.2 7 0.2 -
All external causes
Accidents - - 4 0.1 4 0.3 -
Suicides 3 0.4 1 0.03 4 0.3 0.02
Other cause of death 5 0.6 38 1.1 43 3.6 0.26
Unknown cause of death 7 0.9 32 0.9 39 3.2 0.91
Sum of deaths will not add to overall total since data are only shown for causes with at least two deaths in either group of women.
aP value for chi-square test or, where appropriate, Fisher's Exact Test.
Breast Cancer Research Vol 7 No 2 Le et al.
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Table 4
Proportional hazards regression model: hazard ratio and 95% confidence interval (CI) for mastectomy-treated breast cancer
patients in the Surveillance, Epidemiology, and End Results (SEER) Breast Implant Surveillance Study, 1983–1989 (n = 4385)a
Covariate Distribution of sample Breast cancer mortality Non-breast cancer mortality
n% Hazard ratio 95% confidence
interval Hazard ratio 95% confidence
interval
Implant status
No (referent) 3568 81.4 1.00 - 1.00 -
Yes 817 18.6 0.54 0.43–0.67 0.59 0.41–0.85
Age at diagnosis
< 35 years 163 3.7 1.95 1.42–2.69 0.24 0.09–0.66
35–44 years 805 18.4 1.29 1.07–1.56 0.19 0.12–0.30
45–54 years 1332 30.4 1.02 0.86–1.20 0.35 0.26–0.46
55–64 years (referent) 2085 47.6 1.00 - - -
Race/ethnicity
Non-Hispanic White (referent) 3915 89.3 1.00 - 1.00 -
Non-Hispanic Black 131 3.0 0.90 0.58–1.39 1.58 0.93–2.68
Hispanic 120 2.7 1.37 0.93–2.04 1.22 0.64–2.33
Non-Hispanic Asian 160 3.7 0.86 0.57–1.31 0.68 0.33–1.39
Other/unknown 59 1.4 0.75 0.37–1.50 1.36 0.60–3.07
Stage at diagnosis
Local (referent) 3126 71.3 1.00 - 1.00 -
Regional 1208 27.6 2.28 1.97–2.63 1.86 1.65–2.09
Unstaged 51 1.2 3.80 2.41–5.99 3.35 2.28–4.92
SEER region
San Francisco–Oakland (referent) 1624 37.0 1.00 - 1.00 -
Seattle–Puget Sound 1423 34.1 1.10 0.91–1.32 1.17 0.91–1.51
Iowa 1268 28.9 1.15 0.96–1.38 0.86 0.66–1.13
Year of diagnosis
1983 (referent) 1037 23.7 1.00 - 1.00 -
1985 1003 22.9 1.06 0.88–1.29 0.96 0.73–1.27
1987 1232 28.1 0.97 0.80–1.18 1.05 0.78–1.40
1989 1113 25.4 0.84 0.68–1.04 1.12 0.80–1.56
Grade
Well differentiated (referent) 142 3.2 1.00 - 1.00 -
Moderately differentiated 695 15.9 2.16 1.13–4.13 0.75 0.42–1.34
Poorly differentiated 817 18.6 3.45 1.82–6.53 0.79 0.44–1.40
Undifferentiated 182 4.2 4.97 2.52–9.78 1.23 0.60–2.52
Unknown 2549 58.1 2.41 1.28–4.52 0.85 0.50–1.45
Histology
Ductal (referent) 3253 74.2 1.00 - 1.00 -
Lobular 279 6.4 1.09 0.82–1.44 1.26 0.88–1.81
Mixed ductal and lobular 167 3.8 1.06 0.74–1.53 0.66 0.32–1.33
Other 686 15.6 0.71 0.57–0.89 1.01 0.76–1.34
Available online http://breast-cancer-research.com/content/7/2/R184
R192
sue from the body, thereby decreasing the metabolic rate
and slowing the growth rate of residual breast cancer cells
[35]. These mechanisms may provide important clues in
cancer prevention and warrant further investigation.
Conclusions
With a median of more than 12 years of follow-up on
patients, our population-based study shows that the risk of
breast cancer mortality in patients with breast implants fol-
lowing mastectomy is about one-half of that for patients
without implants, after adjustment for prognostic character-
istics. Although patients in our study received implants in
the 1980s and early 1990s, breast implants continue to be
an integral part of breast reconstruction in breast cancer
patients and have not changed dramatically in design.
Thus, despite an overall decrease in implant use among
breast cancer patients, breast implants remain an important
and commonly used option for women considering recon-
struction. Certainly, further research is needed to explain
the survival differential in women with breast implants and
those without, by examining potentially explanatory factors
such as SES, comorbidity, smoking, or other lifestyle fac-
tors. However, based on this large, representative sample
of breast cancer patients with extensive follow-up, we
found that breast implants following mastectomy do not
appear to confer any survival disadvantage following early-
stage breast cancer in women younger than 65 years old.
Competing interests
The author(s) declare that they have no competing
interests.
Authors' contributions
SLG, DWW, JLS, and CFL implemented the study and
acquired the data. GML, SLG, and CDO participated in the
design and conceptualization of the study. GML performed
the statistical analysis and drafted the manuscript. GML,
SLG, CDO, and THMK participated in the analysis and
interpretation of the data. All authors read and approved
the final manuscript.
Acknowledgements
Data for the SEER Breast Implant Surveillance Study were collected by
the Northern California Cancer Center (contract N01-CN-05224 Modi-
fication Number 12), Seattle-Puget Sound Cancer Registry (contract
N01-CN-05230), and Iowa Cancer Registry (contract N01-CN-05229
Modification Number 11) with support of the National Cancer Institute,
National Institutes of Health. The content of this publication does not
necessarily reflect the views or policies of the US Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
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    • "The standardized mortality ratios for women with implants from Sweden (Lipworth et al., 2007), Denmark (Jacobsen et al., 2004), and Finland (Pukkala et al., 2003) were 3.0 or higher compared with other women in those same countries; this is almost twice the standardized mortality ratios of 1.6 to 1.7for women with implants in the United States (Brinton et al., 2006) or Canada (Villeneuve et al., 2006). Age may also be influential; the greatest increases in suicide associated with implants were in postmenopausal women (Rubin et al., 2010 ) and mastectomy patients , whose average age was 47 years (Le et al., 2005). Two other studies noted that suicide risk was greatest for women who had their first augmentation surgery at the age of 40 or older (Brinton et al., 2006; Villeneuve et al., 2006). "
    Full-text · Article · Apr 2016
    • "Breast cancer is almost always treated with surgery, chemotherapy, radiotherapy, and hormone therapy. Surgical procedures, called mastectomy or lumpectomy, have a role in treating most patients with breast cancer (68). During these procedures, the cancerous lesions are removed from the breast along with some of the surrounding tissue. "
    [Show abstract] [Hide abstract] ABSTRACT: Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include BRCA1, BRCA2, p53, PTEN, CHEK2 and ATM. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.
    Full-text · Article · Jun 2012
    • "This finding is not surprising, given that immediate breast reconstruction can interfere with post-mastectomy radiation therapy and that post-mastectomy radiation can adversely affect the aesthetic outcome of an immediate breast reconstruction [13]. Given the myriad of other subtle differences that can affect the treatment course for patients, it might be impossible to completely control for treatment effects within the context of an observational study, as has been reported by Le and colleagues [1]. Thus, a more desirable approach to assessing the long-term effects of reconstructive surgery might be within the context of a clinical trial, where treatment effects can be more fully taken into account. "
    [Show abstract] [Hide abstract] ABSTRACT: In a large study, published in this issue of Breast Cancer Research, Le and colleagues report that women receiving implants after mastectomies for early-stage breast cancer experience lower breast cancer mortality than women not receiving implants. Assessment of survival patterns among women receiving reconstructive implants is complex given unique patient characteristics, disease attributes, and treatment patterns. The interpretation of reduced mortality from breast cancer must be assessed in light of significantly reduced risks of death from most other causes. In contrast, patients receiving post-mastectomy implants had elevated rates of suicide, consistent with findings among women with cosmetic implants. Additional well-designed investigations are needed to clarify survival patterns among women receiving reconstructive implants.
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