The impact of locoregional treatment on survival of patients with primary metastatic breast cancer
The aim of the study was to investigate the impact of primary tumor locoregional treatment (surgery or/and radiotherapy) on overall survival in patients with primary metastatic breast cancer (PMBC). Materials and Methods: This retrospective study included 295 wo men aged from 23 to 76 years with PMB...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Цитувати: | The impact of locoregional treatment on survival of patients with primary metastatic breast cancer / R. Liubota, V. Cheshuk, R. Vereshchako, O. Zotov, V. Zaichuk, N. Anikusko, I. Liubota // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 75-77. — Бібліогр.: 13 назв. — англ. |
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irk-123456789-1375982020-11-12T10:57:14Z The impact of locoregional treatment on survival of patients with primary metastatic breast cancer Liubota, R. Cheshuk, V. Vereshchako, R. Zotov, O. Zaichuk, V. Anikusko, N. Liubota, I. Short communications The aim of the study was to investigate the impact of primary tumor locoregional treatment (surgery or/and radiotherapy) on overall survival in patients with primary metastatic breast cancer (PMBC). Materials and Methods: This retrospective study included 295 wo men aged from 23 to 76 years with PMBC. Among the 295 patients, the effect of locoregional treatment of primary tumor on survival outcomes was evaluated in 177 women with distant metastases at diagnosis of breast cancer. 35 patient received breast surgery (group 1), 95 patients with PMBC — radiotherapy (group 2) and 47 patients — combination of breast surgery and radiation (group 3). The remaining 118 patients didn’t receive surgery or/and radiotherapy (group 4). All patients received systemic cytotoxic chemotherapy. Results: The groups of patients with PMBC did not differ significantly by age, menstrual function, ER status, Her2 receptor status, site of metastasis and number of metastatic lesions. 2- and 5-year overall survival in patients of group 1 was 54 and 32%, group 2 — 47 and 8%, group 3 — 73 and 18%, whereas in patients from group 4 — 26 and 9%, respectively. The median survival of patients who underwent surgery was 36 months, patients with PMBC who received radiotherapy — 24 months, patients who obtained combination of breast surgery and radiation — 30 months vs 18 months in patients who did not undergo primary tumor locoregional treatment. Conclusions: The results of this study showed a favourable effect of locoregional treatment in patients with PMBC. 2017 Article The impact of locoregional treatment on survival of patients with primary metastatic breast cancer / R. Liubota, V. Cheshuk, R. Vereshchako, O. Zotov, V. Zaichuk, N. Anikusko, I. Liubota // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 75-77. — Бібліогр.: 13 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137598 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Short communications Short communications |
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Short communications Short communications Liubota, R. Cheshuk, V. Vereshchako, R. Zotov, O. Zaichuk, V. Anikusko, N. Liubota, I. The impact of locoregional treatment on survival of patients with primary metastatic breast cancer Experimental Oncology |
| description |
The aim of the study was to investigate the impact of primary tumor locoregional treatment (surgery or/and radiotherapy) on overall survival in patients with primary metastatic breast cancer (PMBC). Materials and Methods: This retrospective study included 295 wo men aged from 23 to 76 years with PMBC. Among the 295 patients, the effect of locoregional treatment of primary tumor on survival outcomes was evaluated in 177 women with distant metastases at diagnosis of breast cancer. 35 patient received breast surgery (group 1), 95 patients with PMBC — radiotherapy (group 2) and 47 patients — combination of breast surgery and radiation (group 3). The remaining 118 patients didn’t receive surgery or/and radiotherapy (group 4). All patients received systemic cytotoxic chemotherapy. Results: The groups of patients with PMBC did not differ significantly by age, menstrual function, ER status, Her2 receptor status, site of metastasis and number of metastatic lesions. 2- and 5-year overall survival in patients of group 1 was 54 and 32%, group 2 — 47 and 8%, group 3 — 73 and 18%, whereas in patients from group 4 — 26 and 9%, respectively. The median survival of patients who underwent surgery was 36 months, patients with PMBC who received radiotherapy — 24 months, patients who obtained combination of breast surgery and radiation — 30 months vs 18 months in patients who did not undergo primary tumor locoregional treatment. Conclusions: The results of this study showed a favourable effect of locoregional treatment in patients with PMBC. |
| format |
Article |
| author |
Liubota, R. Cheshuk, V. Vereshchako, R. Zotov, O. Zaichuk, V. Anikusko, N. Liubota, I. |
| author_facet |
Liubota, R. Cheshuk, V. Vereshchako, R. Zotov, O. Zaichuk, V. Anikusko, N. Liubota, I. |
| author_sort |
Liubota, R. |
| title |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| title_short |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| title_full |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| title_fullStr |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| title_full_unstemmed |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| title_sort |
impact of locoregional treatment on survival of patients with primary metastatic breast cancer |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2017 |
| topic_facet |
Short communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137598 |
| citation_txt |
The impact of locoregional treatment on survival of patients with primary metastatic breast cancer / R. Liubota, V. Cheshuk, R. Vereshchako, O. Zotov, V. Zaichuk, N. Anikusko, I. Liubota // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 75-77. — Бібліогр.: 13 назв. — англ. |
| series |
Experimental Oncology |
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2025-07-10T04:05:31Z |
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| fulltext |
Experimental Oncology 39, 75–77, 2017 (March) 75
THE IMPACT OF LOCOREGIONAL TREATMENT ON SURVIVAL
OF PATIENTS WITH PRIMARY METASTATIC BREAST CANCER
R. Liubota1, *, V. Cheshuk 1, R. Vereshchako1, O. Zotov1, V. Zaichuk1, N. Anikusko2, I. Liubota2
1Department of Oncology, O.O. Bogomolets National Medical University, Kyiv 03115, Ukraine
2Municipal City Clinical Oncological Centre, Kyiv 03115, Ukraine
The aim of the study was to investigate the impact of primary tumor locoregional treatment (surgery or/and radiotherapy) on overall
survival in patients with primary metastatic breast cancer (PMBC). Materials and Methods: This retrospective study included 295 wo men
aged from 23 to 76 years with PMBC. Among the 295 patients, the effect of locoregional treatment of primary tumor on survival outcomes
was evaluated in 177 women with distant metastases at diagnosis of breast cancer. 35 patient received breast surgery (group 1), 95 patients
with PMBC — radiotherapy (group 2) and 47 patients — combination of breast surgery and radiation (group 3). The remaining 118 pa-
tients didn’t receive surgery or/and radiotherapy (group 4). All patients received systemic cytotoxic chemotherapy. Results: The groups
of patients with PMBC did not differ significantly by age, menstrual function, ER status, Her2 receptor status, site of metastasis and
number of metastatic lesions. 2- and 5-year overall survival in patients of group 1 was 54 and 32%, group 2 — 47 and 8%, group 3 —
73 and 18%, whereas in patients from group 4 — 26 and 9%, respectively. The median survival of patients who underwent surgery was
36 months, patients with PMBC who received radiotherapy — 24 months, patients who obtained combination of breast surgery and ra-
diation — 30 months vs 18 months in patients who did not undergo primary tumor locoregional treatment. Conclusions: The results of this
study showed a favourable effect of locoregional treatment in patients with PMBC.
Key Words: primary metastatic breast cancer, surgery, radiotherapy, survival.
Breast cancer (BC) is one of the most com-
mon cancers among women worldwide. In 2012,
BC incidence was 43.3 per 100,000 female population,
1,676,633 new cases and 521,907 deaths from this
disease were registered worldwide, which accounted
for 25.2% of cases and 14.7% of deaths among all
cancers in women [1]. In Europe and United States
of America 5–10% of patients of BC are diagnosed with
primary metastatic disease and median survival ranges
from 18 to 24 months [2]. According to the National
Cancer Registry of Ukraine in 2014 7.0% of patients
were diagnosed with primary metastatic breast cancer
(PMBC) [3]. Treatment of metastatic BC is palliative
and symptomatic and must prolongate survival, control
tumor burden, reduce cancer-related symptoms and
improve quality of life. In recent years, the approach
for the management of PMBC has been revised.
The value of the locoregional treatment (LRT) of the
primary tumor and its impact on distant metastasis and
survival is controversial. Currently, surgical treatment
in this group of patients is used only to prevent and/
or treat local complications. However, results of many
retrospective population-based trials demonstrated
that an intensified multidisciplinary approach combin-
ing systemic therapies with surgery [4, 5], radiation,
and regional chemotherapy may not only prevent local
complications, but prolong survival of such patients
similarly to the benefits observed in renal, colorectal,
ovarian and gastric carcinoma [6–10]. The aim of this
study was to investigate the impact of primary tumor
LRT (surgery or/and radiotherapy) on overall survival
(OS) in patients with PMBC.
MATERIALS AND METHODS
The study included 295 women with PMBC aged
from 23 to 76 years (median age 55 ± 11 years) who
received treatment at the clinic of the Department
of Oncology of the O.O. Bogomolets National Medical
University based at the Kyiv Municipal Clinical On-
cological Center from 2004 to 2006. All women with
histologically proven BC and whose distant metas-
tases are discovered at their first admittance were
included in this study (in total, 295 patients). The
diagnosis was defined according to the International
TNM-classification (6th edition 2002). Patients with iso-
lated involvement of ipsilateral supraclavicular lymph
nodes or contralateral lymph nodes metastases were
excluded from this study.
Among the 295 patients with PMBC, the effect
of LRT of primary tumor on survival outcomes was
evaluated in 177 women with distant metastases
at diagnosis of BC. 35 patient received breast surgery
(group 1), 95 patients — radiotherapy (group 2), and
47 patients — combination of breast surgery and radio-
therapy (group 3). The remaining 118 patients didn’t re-
ceive surgery or/and radiotherapy (group 4). The study
was approved by the Local Medical Ethics Committee.
All patients gave their written informed consent be-
fore inclusion in this study. Patients from group 2 and
3 received radiation therapy delivered by a five-field
technique. Field for conventional radiation treatment
of the breast/chest wall: medial and lateral tangen-
tial fields of the whole breast are irradiated. Upper
bound — lower edge of the clavicular head, i.e. lower
edge of the first rib, lower bound — 1–2 cm inferior
to the breast skin folds, medial margin — body midline
Submitted: November 14, 2016.
*Correspondence: E-mail: lyubota@ukr.net
Abbreviations used: BC — breast cancer; ER — estrogen receptor;
LRT — locoregional treatment; OS — overall survival; PMBC — pri-
mary metastatic breast cancer; PR — progesterone receptor.
Exp Oncol 2017
39, 1, 75–77
SHORT COMMUNICATION
76 Experimental Oncology 39, 75–77, 2017 (March)
and lateral margin — middle axillary line or posterior
axillary line. The target dose was a median absorbed
dose of 50 Gy in 25 fractions in 5 weeks. All patients
received systemic cytotoxic chemotherapy.
Statistical analysis. Statistical significance of dif-
ferences between the treatment group was evaluated
by ANOVA and analysis of contingency tables 2xK type.
Differences were considered statistically significant
at a significance level (p) lower than 0.05. Survival was
analyzed using the Kaplan — Meier method comparing
the elapsed time in months from diagnosis (start of the
study), to death (critical event) due to BC progression,
but not other causes. All statistical calculations were
performed using Statistica 6.0 program.
RESULTS
The Table shows the clinical baseline characte-
ristics of the patients. The study groups did not differ
significantly by age, menstrual function, estrogen
receptor (ER) status, Her2/neu receptor status, site
of metastasis and number of metastatic lesions, in-
dicating the equal distribution of patients in groups
on the above criteria.
Table. Clinicopathological characteristics of BC patients
Characteristic Total Group p
value1 2 3 4
No. % N (%) N (%) N (%) No(%)
Menstrual status > 0.05
Premenopause 101 34 12 (34) 38 (40) 18 (38) 33 (28)
Postmeno-
pause
194 66 23 (66) 57 (60) 29 (62) 85 (72)
Age at diagnosis, years > 0.05
≤ 40 63 21 8 (23) 19 (20) 12 (25,5) 24 (20)
41–69 192 65 21 (60) 56 (59) 31 (66) 84 (71)
≥ 70 40 14 6 (17) 20 (21) 4 (8,5) 10 (9)
Number of metastatic lesions > 0.05
≤ 2 163 55 19 (54) 57 (60) 29 (62) 58 (49)
> 2 132 45 16 (46) 38 (40) 18 (38) 60 (51)
Site of metastasis > 0.05
Visceral 41 14 5 (14) 8 (8.5) 8 (17) 20 (17)
Bone only 61 21 7 (20) 25 (26.5) 11 (23) 18 (15)
Bone + visceral 177 60 23 (66) 61 (64) 28 (60) 65 (55)
Brain 16 5 0 1 (1) 0 15 (13)
Hormone receptor status > 0.05
ER positive 201 68 24 (69) 71 (75) 30 (64) 76 (64)
ER negative 94 32 11 (31) 24 (25) 17 (36) 42 (36)
PR positive 192 65 21 (60) 67 (70.5) 33 (70) 71 (60) > 0.05
PR negative 103 35 14 (40) 28 (29.5) 14 (30) 47 (40)
Her2/neu expression > 0.05
Positive 86 29 10 (29) 22 (23) 13 (28) 41 (35)
Negative 209 71 25 (71) 73 (77) 34 (72) 77 (65)
The median follow-up time of the whole population
was 28 months (in a range 3–75 months). The Figure
shows survival curves of PMBC patients from study
groups according to treatment type.
2- and 5-year OS in patients of group 1 was 54 and
32%, group 2 — 47 and 8%, group 3 — 73 and 18%,
whereas those of patients of groups 4 were 26 and
9%, respectively. The median survival for patients
who underwent surgery was 36 months, patients who
received radiotherapy — 24 months, patients who
were treated by combination of breast surgery and
radiation was 30 months vs 18 months in patients who
did not receive primary tumor LRT (surgery or/and
radiotherapy). That shows the positive impact of LRT
on the prognosis of patients with stage IV BC.
DISCUSSION
The PMBC should be considered as a terminal grade
of chronic disease, and systemic cytotoxic therapy
should be included to treatment protocols of stage
IV BC. The effects of endocrine, cytotoxic, targeted,
or combination treatments in PMBC have been stud-
ied in many prospective clinical trials. Despite initial
response, mostly such patients develop progressive
disease within 12–24 months, the median survival
of endocrine nonresponsive or resistant metastatic
BC is 18–24 months, and less than 5% of patients live
5 years. If a response is observed at all sites, continua-
tion of the effective systemic therapy is reasonable [11].
The role of locoregional therapy in patients with
metastatic BC is largely unexplored. There were none
prospective randomized trials dealing with this topic.
In patients whose tumor is well controlled at distant
sites but is progressing locally, local surgery and/or ra-
diotherapy should be discussed. Traditionally, patients
with PMBC have limited local treatments and palliative
management of uncontrolled local and/or regional dis-
ease (in a form of so-called “toilette mastectomy” or low-
dose radiotherapy) [2]. There are still open questions
regarding the type of breast surgery and indication for
radiotherapy. The biological role for removing the primary
tumor in a case of disease dissemination is debatable.
Several potential advantages have been proposed. By re-
moving the primary tumor, one of the sources of further
metastatic spread is eradicated; this risk of reseeding
is more relevant with the current improvements in sys-
temic treatments. Data from animal studies suggest that
removal of tumor bulk may restore immunocompetence
because the primary tumor seems to modulate the
immune system through release of immunosuppres-
sive factors. A reduction in the number of cancer cells
may also lead to increased efficacy of systemic therapy
by decreasing the risk of emergence of chemoresistant
cells and by removal of necrotic tumor tissue poorly ac-
cessible to drugs. Debulking surgery has been proven
clinically effective in other common solid tumors, such
as ovarian, colorectal, gastric, renal cancers, and malig-
nant melanoma [11].
O
S
0
0.2
0.4
0.6
0.8
1
1.2
0 10 20 30 40 50 60 70 80
Time, months
Group 1
Group 2
Group 3
Group 4
Figure. OS in patients with PMBC analyzed using the Kaplan —
Meier method
In PMBC, radiotherapy of the primary tumor
is frequently combined with breast surgery, making
it difficult to discriminate between effects of surgery
or radiotherapy alone. In terms of locoregional con-
Experimental Oncology 39, 75–77, 2017 (March) 77
trol, primary radiotherapy seems to be as effective
as surgery. In a retrospective study by Bourgier et al.
[12], radiation alone was compared with surgery of the
primary tumor plus radiotherapy. The 3-year OS rates
were 39 and 57%, respectively. Le Scodan et al. [13]
presented a retrospective review of patients with
PMBC at the Renee Cancer Center in France. LRT was
applied to 320 patients: 249 (78%) were treated with
radiotherapy alone, 41 (13%) underwent surgery plus
radiation, and 30 (9%) were treated only with surgery.
The 3-year OS rates were 43.2% in the group with LRT
and 26.7% in the group without LRT. In our study, 2- and
5-year OS in patients who gotten radiotherapy were 47%
and 8%, respectively, and 73 and 18% in patients who
received combination of breast surgery and radiation.
Our study showed the LRT of the intact primary
tumor in PMBC patients improved median survival time
and OS. The pivotal question, which selected patients
would benefit from breast surgery concerning survival,
cannot be answered by the existing retrospective
data by the current meta-analysis. The optimal point
of time and the decision for or against breast surgery
and radiation depending on the response to systemic
therapy remain unclear. Nevertheless, results of mul-
tivariable analyses controlling these confounding
factors, consistently suggest a survival benefit for
optimal LRT of the primary tumor. Some questions
still remain unsolved, including which patients could
benefit most from LRT and what is its optimal timing
and the best systemic cytotoxic treatment regime for
these selected patients. Prospective randomization
studies are needed to validate these findings. While
waiting for data from these studies, LRT for breast
primary tumor can be considered as a relatively inex-
pensive and low morbidity treatment, which can offer
a rapid local control and has a potential for impoving
patient’s survival.
CONCLUSIONS
The optimal management of stage IV BC is unknown,
and thus there is no consensus about the value of sur-
gery in the management of this population. A clinician
and a patient may consider surgical resection of the
primary tumor in this setting for multiple reasons. LRT
of the primary tumor in metastatic BC patients could ex-
ert two major effects: the effect of surgery on OS and its
effect on local disease control. In patients whose tumor
is well controlled at distant sites but progressing locally,
local surgery and/or radiotherapy should be discussed.
The results of this study showed the positive impact
of LRT on the prognosis of patients with PMBC. How-
ever, further research should be aimed on establishing
criteria for selecting patients with PMBC for primary
tumor LRT (surgery or/and radiotherapy).
This research was presented in part at the Advanced
Breast Cancer Third International Consensus Confe-
rence, November 5–7, 2015, Lisbon, Portugal.
ACKNOWLEDGEMENTS
The authors would like to thank the medical per-
sonal of Municipal Clinical Oncological Centre for
professional work on diagnostic, treatment and taking
care of the patients during the research.
CONFLICT OF INTERESTS
The authors declared no conflict of interests.
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