Available via license: CC BY-NC 4.0
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Overall survival after mastectomy versus
breast-conserving surgery with adjuvant radiotherapy
for early-stage breast cancer: meta-analysis
Kiran K. Rajan
1,2,
* , Katherine Fairhurst
1,3
, Beth Birkbeck
1
, Shonnelly Novintan
1
, Rebecca Wilson
1,4
, Jelena Savovic
1,4
,
Chris Holcombe
3
and Shelley Potter
1,5
1
Bristol Medical School, University of Bristol, Bristol, UK
2
Bristol Royal Inrmary, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
3
Linda McCartney Centre, Liverpool University Hospitals NHS Trust, Liverpool, UK
4
NIHR Applied Research Collaboration West (ARC West), University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
5
Bristol Breast Care Centre, North Bristol NHS Trust, Bristol, UK
*Correspondence to: Kiran K. Rajan, 2nd Floor, Learning and Research, Southmead Hospital, Bristol BS10 5NB, UK (e-mail: mb28106@bristol.ac.uk)
Presented as a Spotlight Poster discussion at the San Antonio Breast Cancer Symposium, December 2022 and as an oral presentation at the Association of Breast
Surgery Conference, Belfast, May 2023.
Abstract
Background: Breast-conserving surgery with adjuvant radiotherapy and mastectomy are currently offered as equivalent surgical
options for early-stage breast cancer based on RCTs from the 1970s and 1980s. However, the treatment of breast cancer has evolved
and recent observational studies suggest a survival advantage for breast-conserving surgery with adjuvant radiotherapy. A
systematic review and meta-analysis was undertaken to summarize the contemporary evidence regarding survival after breast-
conserving surgery with adjuvant radiotherapy versus mastectomy for women with early-stage breast cancer.
Methods: A systematic search of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase that identied
studies published between 1 January 2000 and 18 December 2023 comparing overall survival after breast-conserving surgery with
adjuvant radiotherapy versus mastectomy for patients with unilateral stage 1–3 breast cancer was undertaken. The main exclusion
criteria were studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes, and specic breast cancer populations. The
ROBINS-I tool was used to assess risk of bias, with the overall certainty of evidence assessed using the Grading of Recommendations,
Assessment, Development, and Evaluation (GRADE) tool. Studies without critical risk of bias were included in a quantitative meta-analysis.
Results: From 11 750 abstracts, 108 eligible articles were identied, with one article including two studies; 29 studies were excluded from
the meta-analysis due to an overall critical risk of bias, 42 studies were excluded due to overlapping study populations, and three studies
were excluded due to reporting incompatible results. A total of 35 observational studies reported survival outcomes for 909 077 patients
(362 390 patients undergoing mastectomy and 546 687 patients undergoing breast-conserving surgery with adjuvant radiotherapy). The
pooled HR was 0.72 (95% c.i. 0.68 to 0.75, P < 0.001), demonstrating improved overall survival for patients undergoing breast-conserving
surgery with adjuvant radiotherapy. The overall certainty of the evidence was very low.
Conclusion: This meta-analysis provides evidence suggesting a survival advantage for women undergoing breast-conserving surgery with
adjuvant radiotherapy for early-stage breast cancer compared with mastectomy. Although these results should be interpreted with
caution, they should be shared with patients to support informed surgical decision-making.
Received: November 09, 2023. Revised: March 05, 2024. Accepted: March 24, 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/
licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For
commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our
RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Introduction
Breast cancer is the most common cancer worldwide, with over
2.2 million cases diagnosed in 2020
1
. Treatment for early-stage
breast cancer is multimodal and may include chemotherapy,
endocrine therapy, and radiotherapy, but almost all women will
undergo surgery as part of their treatment.
Currently, mastectomy and breast-conserving surgery with
adjuvant radiotherapy (BCS + RT) are offered as comparable
surgical options based on the results of two landmark RCTs that
showed equivalent long-term survival outcomes for the
procedures
2,3
. Since then, treatment for breast cancer has
evolved, with improvements in systemic anticancer therapy and
locoregional treatments
4
, and a recently published large-scale
observational study suggests that BCS + RT may provide a
survival benet compared with mastectomy
5
. If BCS + RT offers
women superior oncological outcomes compared with
mastectomy, this information should be shared with patients as
a key part of the decision-making process and may impact
women’s treatment decisions.
The aim of this review was to systematically identify, appraise,
and summarize the current literature on survival outcomes for
patients undergoing mastectomy and BCS + RT to provide the
BJS Open, 2024, zrae040
https://doi.org/10.1093/bjsopen/zrae040
Systematic Review
most up-to-date evidence to support informed decision-making in
the treatment of early-stage breast cancer.
Methods
Eligibility
All RCTs and observational studies published between 1 January
2000 and 18 December 2023 that compared overall survival for
women undergoing BCS + RT versus mastectomy (with or
without radiotherapy) for primary unilateral unifocal stage 1–3
breast cancer and having surgery as their rst treatment were
eligible for inclusion in the systematic review. Scoping work
suggested that many observational studies included patients
who did not receive adjuvant radiotherapy as part of the BCS +
RT group; only studies for which greater than 95% of the BCS +
RT cohort received adjuvant radiotherapy were therefore
considered eligible for inclusion in the review. Studies published
before 2000 were excluded as they were considered unlikely to
reect current practice. Letters, conference abstracts, reviews,
and grey literature were excluded due to difculty assessing
incomplete information. Studies reporting outcomes for patients
receiving neoadjuvant therapy were excluded, together with
studies specically reporting outcomes for specied breast
cancer groups (for example pregnancy-related breast cancer,
occult primary breast cancer, bilateral breast cancer, and
prespecied rare subtypes of breast cancer). See Table 1. The
titles and abstracts were screened independently by two
reviewers (K.K.R., B.B. or S.N.) and the full texts were obtained if
there was uncertainty. Disagreement was resolved by discussion
with senior members of the team (K.F. and S.P.).
Search strategy
This systematic review was prospectively registered in PROSPERO,
the international prospective register of systematic reviews
(CRD42021248849)
6
, and is reported according to PRISMA
guidelines
7
. The PRISMA checklist is available in the
Supplementary Material. A search of MEDLINE, the Cochrane
Central Register of Controlled Trials (CENTRAL), and Embase
was conducted on 18 December 2023. The search strategy was
developed based on the eligibility criteria in collaboration with a
specialist librarian. The search included terms for ‘breast
cancer’ in combination with terms for surgical procedures of
interest and ‘overall survival’ as the outcome of interest. The
full search strategy is detailed in the Supplementary Methods.
Data extraction
A data extraction form was iteratively developed in Microsoft Excel
by a clinician and a methodologist with expertise in evidence
synthesis (R.W. and J.S.). Data collected included study
characteristics, type of study, type of data collection, aim of study,
study interval, population and setting studied, inclusion and
exclusion criteria, sample size, treatment details, demographic
data, statistical analysis performed, and reported overall survival.
The completed data extraction forms were double-checked by the
second reviewer (S.N.).
Bias assessment
The Risk of Bias 2 (RoB 2)
8
and ROBINS-I
9
tools were used to assess
the risk of bias in RCTs and observational studies respectively. The
bias was evaluated by two reviewers (K.K.R. and S.N.), with any
disagreements resolved by discussion with senior members of
the team (K.F. and S.P.). The Grading of Recommendations,
Assessment, Development, and Evaluation (GRADE) tool
10
was
used to assess the overall certainty of the evidence.
Outcomes
The primary outcome was overall survival for patients undergoing
mastectomy and BCS + RT for early-stage breast cancer.
Statistical analysis
All studies, excluding those considered to be at critical risk of bias,
were included in a quantitative meta-analysis. When studies
reported on the same or overlapping population, such as
registry-based studies, the study with the most recent and largest
population was selected for inclusion. The primary meta-analysis
included all eligible studies and used random effects with a
common-effect inverse-variance model to produce a combined
HR. A xed-effect model was also conducted as a sensitivity
analysis. A total of four subgroup analyses were conducted to
explore survival outcomes for specic patient populations of
interest: studies including patients with triple-negative breast
cancer only; studies reporting outcomes for BCS + RT and
mastectomy without radiotherapy; studies reporting outcomes for
BCS + RT and mastectomy with radiotherapy; and studies of
young patients (dened as those less than 50 years old at
diagnosis). If a study reported outcomes for these dened groups
separately the results were also included in the subgroup
analyses. If studies reported outcomes other than HRs, and no
data transformation was possible, they were excluded. Studies
with unclear or inconsistent numbers of enrolled participants
were also excluded from the meta-analysis. When results were
presented separately in a study, they were combined using
appropriate statistical methods, so that they could be included in
the meta-analysis. Details of this process can be found in the
Supplementary Methods. All analyses were conducted in STATA17
11
.
Table 1 Exclusion criteria
Letters, correspondence, comments, conference reports, abstracts,
and grey literature
Study not primarily comparing survival outcomes for women
undergoing breast-conserving surgery with adjuvant radiotherapy
versus mastectomy for early-stage (1–3) breast cancer with
curative intent
Study published before 1 January 2000
All study participants treated or diagnosed before 1 January 1990
No oncological outcomes reported in the published article
Study not in humans
Study not published in English
Study sample size <10
Studies solely reporting outcomes for specic patient groups
Patients receiving neoadjuvant therapy
Patients with occult breast cancers
Patients with bilateral, multifocal, or multicentric breast cancer
Patients with recurrent breast cancer
Patients with inammatory breast cancer
Patients with pregnancy-related breast cancer
Patients with pre-specied rare subtypes of breast cancers
Patients with hereditary breast cancer
Patients with breast sarcomas
Patients undergoing breast-conserving surgery without adjuvant
radiotherapy (studies excluded if ≤95% of the breast-conserving
surgery with adjuvant radiotherapy cohort received adjuvant
radiotherapy)
Patients not receiving standard of care (for example radical
mastectomy)
2 | BJS Open, 2024, Vol. 8, No. 3
Table 2 Studies included in the meta-analysis
Study Population
setting
No. of
patients
in total
No. of patients
undergoing
breast-conserving
surgery with
adjuvant
radiotherapy
No. of
patients
undergoing
mastectomy
Breast
cancer
stage(s)
Comparison
intervention
Overall
bias
HR (95% c.i.)
Abdulkarim et al.
13
, 2011 Alberta,
Canada
768 319 449 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.92 (0.66, 1.26)
Adkins et al.
14
, 2011 USA 1325 651 674 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.82 (0.68, 0.98)
Almahariq et al.
15
, 2020 USA 231 642 144 263 87 379 1 and 2 Mastectomy
alone
Serious 0.71 (0.69, 0.73)
Bhoo-Pathy et al.
16
, 2015 Asia 1138 366 772 1, 2,
and 3
Mastectomy
with
radiotherapy
Serious 0.60 (0.38, 2.45)
Braunstein et al.
17
, 2015 USA 98 46 52 1, 2,
and 3
Mastectomy
with
radiotherapy
Serious 0.94 (0.36, 2.45)
Cao et al.
18
, 2014 Canada 965 616 349 1 and 2 Mastectomy
with or without
radiotherapy
Serious 0.88 (0.66, 1.18)
Chu et al.
19
, 2022 USA 214 128 125 025 89 103 1 and 2 Mastectomy
with or without
radiotherapy
Serious 0.69 (0.66, 0.72)
Corradini et al.
20
, 2019 Munich,
Germany
7565 6412 1153 1 and 2 Mastectomy
alone
Serious 0.79 (0.66, 0.95)
de Boniface et al.
21
, 2018 Sweden 2767 2338 429 1 and 3 Mastectomy
alone
Serious 0.59 (0.48, 0.73)
de Boniface et al.
22
, 2021 Sweden 48 986 29 367 19 619 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.64 (0.60, 0.68)
De Lorenzi et al.
23
, 2016 Italy 579 193 386 2 and 3 Mastectomy
with or without
radiotherapy
Serious 0.91 (0.52, 1.60)
De-la-Cruz-Ku et al.
24
, 2020 Peru 263 101 162 1 and 2 Not stated Serious 0.79 (0.37, 1.67)
Grover et al.
25
, 2017 USA 150 171 98 952 51 219 1 and 2 Mastectomy
alone
Serious 0.73 (0.70, 0.75)
Hartmann-Johnsen et al.
26
,
2015
Norway 13 015 8065 4950 1 and 2 Mastectomy
with or without
radiotherapy
Serious 0.61 (0.55, 0.67)
Horiguchi et al.
27
, 2002 Japan 228 119 109 1 and 2 Mastectomy
alone
Serious 0.89 (0.36, 2.17)
Kim et al.
12
, 2021 (Korean
Breast Cancer Registry)*
South Korea 45 770 28 623 17 147 1 and 2 Mastectomy
alone
Serious 0.56 (0.51, 0.60)
Kim et al.
12
, 2021 (Asan
Medical Center
database)*
South Korea 10 016 6383 3633 1 and 2 Mastectomy
alone
Serious 0.61 (0.51, 0.73)
Kim et al.
28
, 2011 South Korea 490 125 365 2 Mastectomy
alone
Serious 0.54 (0.28, 1.07)
Lagendijk et al.
5
, 2018 The
Netherlands
129 692 72 993 56 699 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.72 (0.70, 0.74)
Laurberg et al.
29
, 2016 Denmark 813 298 515 1 and 2 Mastectomy
alone
Serious 1.13 (0.86, 1.47)
Magnoni et al.
30
, 2023 Italy 3940 1970 1970 1, 2,
and 3
Mastectomy
alone
Serious 1.10 (0.90, 1.33)
Maishman et al.
31
, 2017 UK 2429 1240 1189 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.79 (0.61, 1.03)
Parker et al.
32
, 2010 USA 202 61 141 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.54 (0.22, 1.34)
Rapiti et al.
33
, 2003 Switzerland 989 780 209 1 Not stated Serious 0.69 (0.46, 1.03)
Ratosa et al.
34
, 2021 Slovenia 1360 1021 339 1 and 2 Mastectomy
alone
Serious 0.94 (0.50, 1.77)
Sayed et al.
35
, 2020 Egypt 434 254 180 1 and 2 Mastectomy
alone
Serious 0.35 (0.15, 0.84)
Sinnadurai et al.
36
, 2019 Malaysia,
Singapore,
and Hong
Kong
3536 1291 2245 1 and 2 Mastectomy
with or without
radiotherapy
Serious 0.81 (0.64, 1.03)
(continued)
Rajan et al. | 3
Results
Study selection
After de-duplication, 11 750 abstracts were identied; 189
underwent full-text review and, of these, 108 papers met the
inclusion criteria. A paper by Kim et al.
12
included separate
analyses on two distinct databases and is therefore counted as
two studies; these are referred to as Kim et al.
12
, 2021 (Korean
Breast Cancer Registry) and Kim et al.
12
, 2021 (Asan Medical
Center database) (see Table 2). No RCTs were identied. A total
of 29 studies
45–73
were excluded from the meta-analysis due to
an overall critical risk of bias; 42 studies
74–115
were excluded due
to overlapping study populations and three studies
116–118
were
excluded due to reporting results incompatible with inclusion in
the meta-analysis. Details regarding study selection are
provided in Fig. 1.
Study characteristics
The 35 studies (11 multicentre observational
studies
17,20,21,27,31,32,34,36,37,41,42
, 10 single-centre observational
studies
12,14,23,24,28,30,35,39,40,44
, and 14 registry-based
observational studies
5,12,13,15,16,18,19,22,25,26,29,33,38,43
) included in
the meta-analysis are summarized in Table 2 and reported
overall survival for 909 077 patients (546 687 patients undergoing
BCS + RT and 362 390 patients undergoing mastectomy with or
without radiotherapy). A single study
30
used a propensity
score-matched patient cohort and another study
23
matched
patients by age, year of surgery, number of positive axillary
lymph nodes, and tumour subtype.
Risk-of-bias assessment
All 35 included studies had a serious overall risk of bias (Table 2).
Most studies (34 of 35 studies) were at high risk of bias due to
confounding. Full details of the risk-of-bias assessment are
provided in Table S1.
Survival outcomes for all studies comparing
breast-conserving surgery with adjuvant
radiotherapy versus mastectomy
The main random-effects model of the 35 included studies
identied an overall survival advantage for patients undergoing
BCS + RT compared with those undergoing mastectomy (pooled
HR 0.72, 95% c.i. 0.68 to 0.75, P < 0.001, I
2
76.3%) (Fig. 2). Similar
results were seen in the xed-effect model sensitivity analysis
(HR 0.70, 95% c.i. 0.69 to 0.71, P < 0.001, I
2
76.3%), but the overall
evidence was deemed to be of very low certainty due to the
serious risk of bias and inconsistency of reported results.
Survival outcomes for breast-conserving surgery
with adjuvant radiotherapy versus mastectomy
for triple-negative breast cancer
A total of nine studies
13,14,16,19,24,32,36,41,44
with a total 26 530 patients
(13 060 patients undergoing mastectomy and 13 470 patients
undergoing BCS + RT) reported survival for patients with
triple-negative breast cancer only, all of which had a serious
overall risk of bias. Similar survival benets were demonstrated for
patients undergoing BCS + RT compared with those undergoing
mastectomy in this group (HR 0.73, 95% c.i. 0.68 to 0.79, P < 0.001, I
2
0.0%), consistent with the main analysis (Fig. S1).
Survival outcomes for breast-conserving surgery
with adjuvant radiotherapy versus mastectomy
with and without radiotherapy
A total of 21 studies
12,13,15,16,20–22,25,27–30,34,35,39,40,42,44,101,113
including
a total of 688 394 patients compared overall survival for 467 283
patients undergoing BCS + RT versus 221 111 patients undergoing
mastectomy without radiotherapy. A study
101
excluded from the
main meta-analysis due to overlapping registry data was included
in this subgroup analysis due to the other study
38
not explicitly
reporting outcomes for mastectomy without radiotherapy. All
studies had a serious overall risk of bias. Again, similar survival
benets were seen for patients undergoing BCS + RT compared
Table 2 (continued)
Study Population
setting
No. of
patients
in total
No. of patients
undergoing
breast-conserving
surgery with
adjuvant
radiotherapy
No. of
patients
undergoing
mastectomy
Breast
cancer
stage(s)
Comparison
intervention
Overall
bias
HR (95% c.i.)
Sun et al.
37
, 2020 China 4262 404 3858 2 Mastectomy
with or without
radiotherapy
Serious 1.19 (0.72, 1.99)
Vasilyeva et al.
38
, 2023 Canada 13 914 8228 5686 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.72 (0.65, 0.80)
Wan et al.
39
, 2021 China 7905 2956 4949 1, 2,
and 3
Mastectomy
with or without
radiotherapy
Serious 0.58 (0.50, 0.68)
Wang et al.
40
, 2018 China 6137 1296 4841 1 and 2 Mastectomy
alone
Serious 0.62 (0.40, 0.97)
Wen et al.
41
, 2020 Australia 214 168 46 1, 2,
and 3
Mastectomy
with
radiotherapy
Serious 0.48 (0.18, 1.28)
Yoo et al.
42
, 2019 South Korea 1074 676 398 2 and 3 Mastectomy
alone
Serious 0.60 (0.30, 1.20)
Yood et al.
43
, 2008 USA 1616 639 977 1 and 2 Not stated Serious 1.00 (0.82, 1.21)
Zumsteg et al.
44
, 2013 New York,
USA
646 448 198 1 and 2 Mastectomy
alone
Serious 0.92 (0.53, 1.59)
*Paper by Kim et al.
12
included separate analyses on two distinct databases and is therefore counted as two studies.
4 | BJS Open, 2024, Vol. 8, No. 3
with patients undergoing mastectomy without radiotherapy (HR
0.70, 95% c.i. 0.65 to 0.75, P < 0.001, I
2
84.2%) (Fig. S2).
A total of nine studies
13,16,17,22,39,41,82,93,113
including a total of 218
392 patients specically reported overall survival for women
undergoing BCS + RT (194 368 patients) versus mastectomy with
radiotherapy (24 024 patients). Three studies
82,93,113
that were
excluded from the main meta-analysis due to overlapping registry
data were included in this subgroup analysis due to the other four
studies
15,19,25,43
not explicitly reporting outcomes for patients
undergoing mastectomy and radiotherapy. All studies had a
serious overall risk of bias. A survival benet was also seen for
patients undergoing BCS + RT compared with patients undergoing
mastectomy with radiotherapy (HR 0.74, 95% c.i. 0.66 to 0.83, P <
0.001, I
2
69.4%) (Fig. S3).
Survival outcomes for breast-conserving surgery
with adjuvant radiotherapy versus mastectomy
for young patients
A total of ten studies
16,18,26,29,31,36,75,93,94,113
including a total of
63 976 patients specically reported overall survival for younger
women (less than 50 years old) undergoing BCS + RT (36 658
patients) versus mastectomy (27 318 patients). Three studies
75,93,94
that were excluded from the main meta-analysis due to
overlapping registry data were included in this subgroup analysis
Databases searched:
MEDLINE, the Cochrane Central
Register of Controlled Trials
(CENTRAL), and Embase
Excluded articles n = 11 561
Letters, conference abstracts, or editorials n = 2265
Not primarily comparing survival outcomes for
breast-conserving surgery with adjuvant
radiotherapy versus mastectomy n = 8933
Sample size <10 n = 22
Solely using neoadjuvant therapy n = 157
Published before 1 January 2000 n = 19
Study not in humans n = 3
Bilateral, multifocal, or multicentric n = 20
Not published in English n = 13
Specified patient groups n = 124
Not standard care n = 3
No full-text article found n = 2
Excluded articles n = 81
No overall survival reported n = 39
Study population recruited before 1990 n = 8
Not standard care n = 11
Recurrent breast cancer n = 4
Not primarily comparing survival outcomes for
breast-conserving surgery with adjuvant
radiotherapy versus mastectomy n = 8
Subcohort of another published article n = 1
Paper including stage 0 or 4 breast cancer n = 3
Incomplete results n = 7
Excluded studies from meta-analysis n = 74
Critical risk of bias n = 29
Overlapping study populations n = 42
Incompatible results n = 3
Titles and abstracts screened:
n = 11 750
Full-text articles screened:
n = 189
Full-text articles included:
n = 108
Studies included in analysis:
n = 35*
Included Identification
Screening
Fig. 1 PRISMA ow diagram of the systematic review
*Paper by Kim et al.
12
included separate analyses on two distinct databases and is therefore counted as two studies.
Rajan et al. | 5
due to the other studies
12,15,19,25
not explicitly reporting outcomes
for younger patients. All studies had a serious overall risk of bias.
Again, a survival benet for young women undergoing BCS + RT
compared with those undergoing mastectomy (HR 0.82, 95% c.i.
0.73 to 0.93, P = 0.002, I
2
68.0%) was seen (Fig. S4).
Discussion
Mastectomy and BCS + RT have long been accepted as equivalent
oncological options on the basis of landmark RCTs from the 1970s
and 1980s
2,3
. However, the present meta-analysis of 35
contemporary studies published between 1 January 2000 and
18 December 2023 suggests that BCS + RT may confer a survival
benet for patients compared with mastectomy in the context of
modern systemic and locoregional management of early-stage
breast cancer. These results were consistent in studies of
triple-negative breast cancer, in studies of patients less than
50 years old, and irrespective of whether or not patients with
mastectomy received radiotherapy. The evidence overall was
considered to be of very low certainty due to the high risk of bias in
the included studies and high heterogeneity. Therefore, these
ndings should be interpreted with caution.
Despite this, the present analysis adds to an emerging body of
evidence that consistently suggests superior survival outcomes for
patients undergoing BCS + RT compared with those for patients
undergoing mastectomy
119
. Another recent meta-analysis
120
Note: Weights are from random-effects model
0.25 0.5 1.0 2.0 4.0
Abdulkarim et al. (2011)
Adkins et al. (2011)
Almahariq et al. (2020)
Bhoo-Pathy et al. (2015)
Braunstein et al. (2015)
Cao et al. (2014)
Chu et al. (2022)
Corradini et al. (2019)
De Lorenzi et al. (2016)
De-la-Cruz-Ku et al. (2020)
Grover et al. (2017)
Hartmann-Johnsen et al. (2015)
Horiguchi et al. (2002)
Kim et al. (2011)
Kim et al. (2021)-AMC
Kim et al. (2021)-KBCR
Lagendijk et al. (2018)
Laurberg et al. (2016)
Magnoni et al. (2023)
Maishman et al. (2017)
Parker et al. (2010)
Rapiti et al. (2003)
Ratosa et al. (2021)
Sayed et al. (2020)
Sinnadurai et al. (2019)
Sun et al. (2020)
Vasilyeva et al. (2023)
Wan et al. (2021)
Wang et al. (2018)
Wen et al. (2020)
Yoo et al. (2019)
Yood et al. (2008)
Zumsteg et al. (2013)
de Boniface et al. (2018)
de Boniface et al. (2021)
Overall, DL (P < 0.001; l 2 = 76.3%)
0.92
0.82
0.71
0.60
0.94
0.88
0.69
0.79
0.91
0.79
0.73
0.61
0.89
0.54
0.61
0.55
0.72
1.13
1.10
0.79
0.54
0.69
0.94
0.35
0.81
1.19
0.72
0.58
0.62
0.48
0.60
1.00
0.92
0.59
0.64
0.72
(0.66, 1.26)
(0.68, 0.98)
(0.69, 0.73)
(0.38, 0.95)
(0.36, 2.45)
(0.66, 1.18)
(0.66, 0.72)
(0.66, 0.95)
(0.52, 1.60)
(0.37, 1.67)
(0.70, 0.75)
(0.55, 0.67)
(0.36, 2.17)
(0.28, 1.07)
(0.51, 0.73)
(0.51, 0.60)
(0.70, 0.74)
(0.86, 1.47)
(0.92, 1.33)
(0.61, 1.03)
(0.22, 1.34)
(0.46, 1.03)
(0.50, 1.77)
(0.15, 0.84)
(0.64. 1.03)
(0.72, 1.99)
(0.65, 0.80)
(0.50, 0.68)
(0.40, 0.97)
(0.18, 1.28)
(0.30, 1.20)
(0.82, 1.21)
(0.53, 1.59)
(0.48, 0.72)
(0.60, 0.68)
(0.68, 0.75)
1.65
3.57
7.86
0.89
0.23
1.92
7.67
3.53
0.62
0.36
7.78
5.97
0.26
0.44
3.59
6.53
7.86
2.16
3.53
2.24
0.25
1.13
0.50
0.27
2.57
0.75
5.73
4.36
0.96
0.22
0.41
3.32
0.66
3.03
7.18
100.00
Study (95% c.i.)HR
Weight
(%)
Fig. 2 Forest plot of HRs for overall survival for breast-conserving surgery with adjuvant radiotherapy versus mastectomy
AMC, Asan Medical Center database; KBCR, Korean Breast Cancer Registry; DL, DerSimonian and Laird Method.
6 | BJS Open, 2024, Vol. 8, No. 3
including all studies published up to October 2021 similarly showed
improved survival for BCS + RT, with a relative risk of 0.64 (95% c.i.
0.55 to 0.74). The present study, by contrast, only included studies
published between 1 January 2000 and 18 December 2023, with no
study cohort solely treated before 1 January 1990, to ensure
patients received modern treatments for breast cancer. The
ndings of the present study are consistent with a recent
meta-analysis of 25 population cohort studies published from 2010
and onward, which also showed BCS + RT to be associated with
better overall survival (HR 1.34, 95% c.i. 1.20 to 1.51) and breast
cancer-specic survival (HR 1.38, 95% c.i. 1.29 to 1.47) compared
with mastectomy
121
.
Similarly consistent results have been reported for specic
patient subgroups. For example, a meta-analysis of seven
studies
122
exploring oncological outcomes for breast-conserving
surgery versus mastectomy for patients with triple-negative breast
cancer found a signicantly lower mortality for breast-conserving
surgery, as well as lower rates of locoregional recurrence and
distant metastases. However, unlike the present study, only a
minority of included studies reported outcomes for patients
having adjuvant radiotherapy after mastectomy. While a
meta-analysis of ve studies exploring survival for patients under
40 years old undergoing BCT + RT versus mastectomy reported no
signicant survival advantage (HR 0.90, 95% c.i. 0.81 to 1.00, P =
0.150) for the BCS + RT group
123
, the present study that included
patients receiving modern treatments from 10 studies did suggest
a survival benet for this subgroup. Therefore, it is possible that
the earlier review
123
was underpowered to detect a difference
between the groups. The HR and 95% c.i. in the present study (HR
0.82, 95% c.i. 0.73 to 0.93, P = 0.002) remain closer to 1.00,
indicating a potentially smaller, but still statistically signicant,
survival benet for BCS + RT for young patients.
The mechanism for the survival benets of BCS + RT compared
with mastectomy is unclear. Improvements in systemic anticancer
treatment and locoregional therapies in recent years may partially
explain the benets seen, but are unlikely to be the only driver for
the survival advantage that is consistently demonstrated for BCS +
RT; another potential explanation may be that breast-conserving
surgery represents a smaller surgical insult, with fewer
complications
124
and less immune impairment, which is
correlated with decreased proliferation of tumour cells and
metastatic seeding
125,126
. Although the exact mechanism is not
completely understood
127
, the present meta-analysis supports the
hypothesis that more radical surgery in the form of total
mastectomy is associated with worse overall survival.
Although the present meta-analysis provides further evidence to
support survival benets for BCS + RT compared with mastectomy,
the results should be interpreted with caution. In the main analysis,
signicant heterogeneity between studies was seen. The included
studies were selected from a time span of approximately 24 years
and include different geographical locations, patient populations,
study designs, such as registry-based versus single-institute
retrospective observational reviews, and selection criteria for
included patients. All of the studies included in the present review
are observational, so there are likely to be inherent biases
regarding the ways in which patients were selected for BCS + RT
versus mastectomy. Patients are not randomized to treatment
groups and therefore there may be many potential confounders,
not all of which can be adjusted for in multivariable analyses.
Important potential confounders, including socio-economic
status, educational level, hospital volume, and geographical
location, have been identied in a more detailed database
128
, and
one North American study suggested that the cost of surgery was
one of the main factors inuencing women’s decision-making
regarding the treatment of breast cancer
129
. Most studies did not
adjust for all of these potential confounders, often because these
data were not collected or available in the data set used. This is
reected in the risk-of-bias assessment, with all but one study
having a severe risk of confounding. However, the consistent
ndings of this and other systematic reviews, in combination with
the ndings of large-scale studies
5,38
, suggest that these ndings
warrant further consideration.
The potential survival benets highlighted in the present study
have important implications for informed consent and surgical
decision-making for patients with early-stage breast cancer. If the
oncological outcomes after mastectomy are indeed inferior to
those after BCS + RT, mastectomy should no longer be offered as
an equivalent treatment option for those patients suitable for
BCS + RT. However, more high-quality evidence is needed. RCTs
comparing surgical techniques in this setting are no longer feasible
or ethical, so well-designed prospective observational cohort
studies, with careful consideration of potential confounders, will
be needed to generate much-needed data. As large numbers of
patients will need to be followed up over an extended interval of
time, prospective studies involving linkage to routinely collected
data sets may be one way in which this could be achieved.
The present review adds to the growing body of evidence
suggesting that BCS + RT may be associated with a survival
advantage compared with mastectomy for patients with
early-stage breast cancer. While these ndings must be
interpreted with caution due to the high risk of bias associated
with observational data, the consistency of ndings across
multiple studies is increasingly compelling. In addition to
mastectomy offering potentially worse long-term survival
compared with BCS + RT, mastectomy has a higher rate of
complications
124
and women undergoing mastectomy report
worse quality of life than those undergoing BCS + RT, even if
reconstruction is performed
130
. Therefore, these data should be
discussed and shared with all patients who require breast cancer
surgery to help them make fully informed decisions about their
treatment options.
Funding
This research received no specic grant from any funding agency
in the public, commercial, or not-for-prot sectors. This work was
supported by the National Institute for Health and Care Research
(NIHR) Biomedical Research Centre at University Hospitals Bristol
and Weston NHS Foundation Trust and the University of Bristol.
S.P. is an NIHR Clinician Scientist (CS-2016-16-019) and K.F. is an
NIHR Academic Clinical Lecturer (CL-2020-25-002). J.S. and
R.W.’s time was partly supported by the NIHR Applied Research
Collaboration West (ARC West) at University Hospitals Bristol
and Weston NHS Foundation Trust. The views expressed are
those of the authors and not necessarily those of the NIHR or
the Department of Health and Social Care.
Author contributions
Kiran K. Rajan (Conceptualization, Investigation, Methodology,
Validation, Writing—original draft), Katherine Fairhurst
(Supervision, Methodology, Writing—review & editing), Beth
Birkbeck (Investigation, Methodology, Writing—review &
editing), Shonelly Novintan (Investigation, Methodology, Writing
—review & editing), Rebecca Wilson (Conceptualization,
Methodology, Writing—review & editing), Jelena Savovic
Rajan et al. | 7
(Conceptualization, Methodology, Writing—review & editing),
Chris Holcombe (Conceptualization, Writing—review & editing),
and Shelley Potter (Conceptualization, Funding acquisition,
Supervision, Methodology, Writing—review & editing)
Disclosure
The authors declare no conict of interest.
Supplementary material
Supplementary material is available at BJS Open online.
Data availability
The authors conrm that the data supporting the ndings of this
study are available within the article and its Supplementary
material.
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