ORIGINAL ARTICLE

Malignant Phyllodes Tumor of the Breast: Treatment

and Prognosis
Jerzy Mitus, MD, PhD,* Marian Reinfuss, MD, PhD,† Jerzy W. Mitus, MD, PhD,*,‡
Jerzy Jakubowicz, MD, PhD,† Pawel Blecharz, MD, PhD,§
Wojciech M. Wysocki, MD, PhD,* and Piotr Skotnicki, MD, PhD*
*Department of Surgical Oncology, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute,
Krakow Branch, Krakow, Poland; †Department of Radiotherapy, Centre of Oncology, Maria
Skłodowska-Curie Memorial Institute, Krak ow Branch, Krakow, Poland; ‡Department of Anatomy,
ow, Poland; §Department of Gynaecological Oncology,
Collegium Medicum, Jagiellonian University, Krak
Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krak
ow Branch, Krakow, Poland

n Abstract: Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast
(MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant
radiotherapy have been controversial. We report a single institution’s experience with MPTB. We discuss controversial ther-
apeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean
age was 50 years (21–76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total
mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins
were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS
margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of
disease (NED) after 5 years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in
patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The
5-year NED survival rates in BCS (tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin <1 cm) groups
were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if
tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are
<1 cm. n
Key Words: breast sarcoma, malignant neoplasm, phyllodes tumor, prognosis, treatment

M alignant phyllodes tumor of the breast (MPTB)

constitutes <1% of breast neoplasm (1–4).
According to the Cancer Surveillance Program of Los
Angeles County (1972–1989), the average annual age-
adjusted incidence of MPTB was 2.1 per million
women (5). According to the Surveillance, Epidemiol-
ogy and End Results Program (SEER) data registry
(2000–2004), ~500 women are annually diagnosed
with MPTB in the United States (6).
Surgery remains the mainstay of the treatment in
patients with MPTB, but the extent of surgery has
been a subject of debate (2,3,7–12). Historically, total
Address correspondence and reprint requests to: Jerzy W. Mitus, MD,
PhD, Department of Surgical Oncology, Centre of Oncology, Maria Skłodo-
wska-Curie Memorial Institute, Krakow Branch, ul. Garncarska 11, Krakow
31-115, Poland, or e-mail: jerzy.mitus@gmail.com
DOI: 10.1111/tbj.12333
© 2014 Wiley Periodicals, Inc., 1075-122X/14
The Breast Journal, 2014 1–6
mastectomy was the treatment of choice; however,
since the 1980s, the number of patients treated with
breast conserving surgery (BCS) has risen (2,3,5,7–
18). In the medical literature, the clear resection mar-
gin, not the type of surgery, has been identified as the
key factor responsible for the low local recurrence rate
of MPTB. However, the appropriate width of tumor-
free margins is still a matter of debate (2–4,7–
9,13,16,19,20). The controversy regarding the role of
adjuvant radiotherapy is likely a result of the low inci-
dence of MPTB and, until recently, the low number of
patients managed in a multi-disciplinary manner
(2,3,5,7–9,11,12,15–18,21).
The purpose of this study was to present our expe-
rience with total mastectomy and BCS with or with-
out adjuvant radiotherapy in the treatment of MPTB
patients. We also discuss the controversial aspects of
MPTB.
2 • mitus et al.

MATERIALS AND METHODS RESULTS

Between January 1980 and April 2008, 215 women Table 1 shows patient characteristics and tumor
with phyllodes tumor of the breast were treated at the characteristics for the total mastectomy and BCS
Center of Oncology in Krak ow (COK). All histologic groups. There were no significant differences between
slides were re-examined, and the diagnosis of MPTB the two groups with regard to age and tumor size (log
was made according to the World Health Organiza- rank test, p > 0.05).
tion criteria: predominantly infiltrating margins, very The 5-year NED survival rate in all patients was
high stromal cellularity, at least 10 mitoses per 10 82.9% (58/70). Five-year NED survival rates were as
high-power fields, and severe cellular atypia (1). Our follows: 84.2% (32/38) for patients <50 years of age
study focuses on a group of 70 (32.6%) patients with versus 81.3% (26/32) for patients ≥50 years of age;
MPTB. 85% (34/40) for patients with smaller (<5 cm)
The mean age of 70 patients with MPTB was tumors versus 80% (24/30) for patients with larger
50 years (21–76 years). Thirty eight (54.3%) patients (≥5 cm) tumors; 82.3% (28/34) for patients who
were <50 years of age, and 32 (45.7%) were underwent mastectomy versus 83.3% (30/36) for
≥50 years of age. Tumor size, defined as the maximal those who underwent BCS or BCS with irradiation.
dimension of the tumor as reported in the pathology The 5-year NED survival rate was identical (83.3%)
report, ranged from 2 to 8 cm (mean 6 cm, median in patients treated with BCS (1–2 cm tumor-free mar-
5 cm). Tumor measurements were as follows: <5 cm gins) and BCS with irradiation (<1 cm tumor-free
in 40 (57.1%) patients, 5–7 cm in 26 (37.2%) margins).
patients, and over 7 cm in 4 (5.7%) patients. Figures 1, 2, and 3 present survival curves in
All 70 MPTB patients underwent surgery. Thirty- patient groups defined by age, tumor size, and type of
four (48.6%) patients were treated with total mastec-
tomy. In 32 (45.7%), total mastectomy was the
primary surgical choice; in the remaining 2 (2.3%) Table 1. Patients and Tumor Characteristics in
patients, BCS was attempted, but due to involved Malignant Phyllodes Tumor of the Breast Treated
with Total Mastectomy or Breast Conserving
margins, salvage total mastectomy was performed.
Surgery
Thirty-six (51.4%) patients underwent BCS (either
lumpectomy or wide local excision). In all patients, Treatment (no. of patients, %)
resection margins were free of tumor; in 30 patients
Characteristics Total mastectomy Breast conserving surgery
(83.3%) the width of the tumor-free margin ranged
between 1 and 2 cm, but in 6 patients it was less than Age
<50 years 18 (52.9) 20 (55.6)
1 cm (range 0.3–0.8 cm). Those 6 patients with ≥50 years 16 (47.1) 16 (44.4)
tumor-free margins less than 1 cm were irradiated. A Tumor size
<5 cm 19 (55.9) 21 (58.3)
dose of 5,040 cGy in 28 fractions over 5 weeks was 5–7 cm 13 (38.2) 13 (36.1)
delivered to the whole breast using a tangential tech- >7 cm 2 (5.9) 2 (5.6)
Total 34 (100.0) 36 (100.0)
nique; this was followed by a boost to the tumor bed
with 2 cm margins (1,000 cGy in 5 fractions). No
regional lymph node metastases were diagnosed in the 100
90,6
90 86,8 84,2 84,2
treated group. 89,5
80
All patients were followed up for at least 5 years. 81,8 81,8 81,8
NED survival (%)

70
They were examined every 3 months during the first 60
< 50 (n = 38)
3 years and every 6 months thereafter. The median 50 ≥ 50 (n = 32)
follow-up duration was 82 months (mean: 40
30
121 months) and ranged from 61 to 394 months.
20
Statistical significance of the observed differences 10
was set at p ≤ 0.05 and determined by the log rank 0
test (22). Five-year survival without evidence of dis- 0 12 24 36 48 60
months after treatment
ease (NED) was used as the end-point for analysis and
was estimated using the Kaplan–Meier method (23). Figure 1. Treatment outcomes in two age groups.
 Malignant Phyllodes Tumor of the Breast • 3

100 DISCUSSION
90 87,5
90 85 85
80 In this study, we report experience with MPTB
80 80
patients in a single institution. The malignant type of
NED survival (%)

70
60 phyllodes tumor constituted 32.6% of all breast
< 5 cm
50 ≥ 5 cm phyllodes tumor patients treated in the COK between
40 1980 and 2008. In the medical literature, the rate of
30
MPTB varies from 8.9% to 30.7% (2,13,14,19,24–
20
26).
10
0
0 12 24 36 48 60
months after treatment
Survival

Figure 2. Treatment outcomes in two tumor size groups.

Five-year NED survival in the analyzed group of
MPTB patients was 82.9%; this is in concordance
with the rates reported in the literature (60–90%)
100
90
91,7
86,1 (2,7,9,21,27–29).
83,3 83,3
80
88,2 In our group, neither age nor tumor size signifi-
82,3 82,3
70 cantly influenced survival rate (Figs. 1 and 2). The
NED survival (%)

60
50
40
30
20
10
0
0 12 24 36
months after treatment
Figure 3. Treatment outcomes in two types of surgery groups.
surgery. There were no statistically significant differ-
ences between any of the curves.
At 5-year follow-up, 12 (17.1%) patients died: 2
(2.8%) from intracranial hemorrhage (at 31 and
37 months after surgery with no signs of MPBT recur-
rence) and 10 (14.3%) from distant metastases (to the
lungs in six patients, brain in three patients, and liver
and bones in one patient); there were no signs of local
MPTB recurrence seen in any of the patients. Distant
metastases were seen on average 23 months (18–
35 months) after surgery. Mean survival time from
the diagnosis of distant metastases was 7 months (3–
17 months). In all patients with metastases, multidrug
chemotherapy was instituted (doxorubicin plus cyclo-
phosphamide in 2 patients, doxorubicin plus cisplatin
in 5 patients, and doxorubicin plus ifosfamide in 3
patients). In one patient, complete remission of lung
lesions was seen; in four patients, at least 50% remis-
sion of lung, liver, and bone metastases was observed.
In two patients, palliative brain irradiation for brain
metastases was performed (20 Gy in 5 fractions).
However, no evident neurological improvement was
noted.
BCS or BCS + RT
(n = 36) majority of reports confirm this observation; only sin-
total mastectomy
(n = 34)
gle studies suggested poorer prognosis in older
patients and/or in patients with greater tumor size
(2,7–9,11,12,16,17,19,21,25,30).
Our analysis showed that the extent of the surgical
48 60
procedure (total mastectomy versus BCS) was not
associated with survival (Fig. 3; 5-year NED survival
was 82.4% (28/34) in patients who underwent mas-
tectomy and 83.3% (30/36) in patients who had BCS
or BCS with adjuvant irradiation). These observations
are totally in concordance with the outcomes
reported by others, who also showed no significant
difference in survival in primary BCS versus patients
who underwent mastectomy (3,4,8,10,11,13,17,18).
Interestingly, identical 5-year NED survival rates
(83.3%) were seen in patients who underwent BCS
without irradiation (i.e. in BCS patients with tumor-
free resection margins ≥1 cm) and in those who had
BCS with irradiation (i.e. in BCS patients with
tumor-free resection margins <1 cm). In the MacDon-
ald et al. study (SEER Program), mastectomy was
performed in 428 women (52%), and wide excision
or lumpectomy was performed in 393 (48%) patients.
With a median follow-up of 5.7 years, course-specific
survival (CSS) was 91% at 5 years, and wide excision
was associated with equivalent or improved CSS
compared to mastectomy on univariate and multivari-
ate analyses (11). It should be emphasized that in
recent years, the ratio of patients with MPTB who
are scheduled for BCS has constantly risen and cur-
rently reaches up to 50% (2–4,9,11,13,14,16–19,
25,27,30–32).
4 • mitus et al.
Metastases
At 5-year follow-up, 10 (14.3%) of 70 patients
died from disseminated MPTB. The incidence of local-
ized lesions (lungs, brain, liver, and bones) as well as
metastatic lesions is in concordance with the data
reported in the medical literature (9–40%)
(2,7,8,11,16,27,28,31,33).
In our group, distant metastases were observed, on
average, 16 months after surgery; in other reports, the
interval between surgery and dissemination was
14 months (Abdall and Sakr), 15 months (Barrio
et al.), 26 months (Kapiris et al.), and 53 months
(Asoglu et al.) (16,25,27,30). The mean survival from
the diagnosis of metastases was 7 months in our
group; Abdall and Sakr reported 5 months (27). Che-
motherapy was proven to have minimal impact on
survival (4,7). There are reports advocating adjuvant
chemotherapy in selected patients with MPTB (selec-
tion criteria include younger age, greater tumor size,
and rapidly growing tumor), but this approach is
widely criticized (3,4,7,9,11,14,21,30).
Local Recurrences and the Extent of Surgery
In our group, no local recurrence of MPTB was
seen; however, in the literature, local recurrences are
observed in 9–36% of MPTB patients (2,3,7–
9,16,18,28,30,31,33,34). Belkacemi et al. of the Rare
Cancer Network study demonstrated that at 5 years
of follow-up, 35% (34/98) of patients with borderline
or MPTB developed local recurrence (33). Pezner
et al. found that 21% of 169 patients with MPTB
undergoing wide local excision developed local recur-
rence after 5 years (9). Both these studies are limited
by the lack of histologic examination of the surgical
margins. Chaney et al. and Asoglu et al. reported that
local control rate decreases with increasing tumor size,
but is not related to the extent of surgery (3,16). The
majority of authors claim that tumor size is not signif-
icantly related to the rate of local recurrence
(2,3,8,13,17,18,25–27,35).
Undoubtedly, the presence of tumor cells in the
resection margin is a strong prognostic factor for local
recurrence in MPTB patients (2,3,7,9,13,16,17,20,21,
25–27,30,31,35). Therefore, it is uniformly accepted
that BCS with tumor-free margins is the treatment
of choice for MPTB; mastectomy is necessary if
tumor-free margins cannot be obtained by BCS
(3,7,11,13,15–17,21,30–32,35). Asoglu et al. showed
that narrow surgical margins significantly increased
local recurrence rate (but no relation between type of
surgery and recurrence rate was observed in this
study) (16). Taira et al. stated that in the case of posi-
tive margins after excision of phyllodes tumor, re-exci-
sion is recommended (35). Telli et al. emphasized that
excision of phyllodes tumor with narrow tumor-free
margins warrants re-excision to obtain ≥1 cm margins
(7). Currently, most authors agree that ≥1 cm tumor-
free margins are necessary (7,13,31).
There were no local recurrences in our group, and
patients were operated on with tumor-free margins. In
64 (91.4%) patients, the width of tumor-free margins
was ≥1 cm (34 patients underwent total mastectomy
and 30 underwent BCS); in the 6 (8.6%) patients who
underwent BCS and adjuvant radiotherapy, the mar-
gins width was 0.3–0.8 cm.
Role of Adjuvant Radiotherapy
The role of adjuvant breast or chest wall radiother-
apy in patients with MPTB is controversial (1–3,7–
9,11,28,31,33,34,36,37). Unfortunately, the role of
adjuvant irradiation in these patients has not been
extensively evaluated. This is likely due to the rarity
of MPTB and the low number of patients who
received adjuvant radiotherapy (less than 10%)
(2,3,6,11,16,17,33,36).
The analysis of SEER data showed that the use of
adjuvant radiotherapy was related to better cause-
specific survival compared to surgery alone in 821
patients with MPTB; however, in this series only 9%
of patients underwent irradiation, and additional
patients selected for radiotherapy were those with lar-
ger tumors with narrow or involved margins (11).
Pezner et al. claimed that adjuvant radiotherapy
should be considered in MPTB patients if they under-
went lumpectomy for tumors ≥2 cm or mastectomy
for tumors ≥10 cm (9). Chaney et al. noted that adju-
vant radiotherapy is recommended for MPTB after
BCS and after mastectomy (if the risk of local recur-
rence is deemed high, i.e., positive margins, margins
<0.5 cm or uncertain margins, tumor size >10 cm or
recurrent disease) (36). The same experts have sug-
gested that adjuvant irradiation should be considered
in patients for whom tumor-free margins cannot be
attained after margin-positive mastectomy (3, 7, 28,
38).
It is known that adjuvant radiotherapy decreases
the risk of local recurrence in MPTB patients

(2,10,11,16,28,31,33). Belkacemi et al. conducted a
retrospective study with 443 patients with phyllodes
tumor (there were 159 MPTB and borderline phyll-
odes tumors combined). Adjuvant radiotherapy
decreased local recurrence rates and was the only
favorable independent prognostic factor in the multi-
variate analysis (33). In the prospective study pre-
sented by Barth et al., 16 patients with borderline
phyllodes tumors and 30 patients with MPTB under-
went BCS (with tumor-free margins) and were treated
with adjuvant radiotherapy. After a median follow-up
of 56 months, no local recurrence was seen in all 46
patients. Sixteen patients from this study had resec-
tion margins <1 cm; in the authors’ opinion, the
absence of local recurrence in these patients indicates
that the addition of radiotherapy allowed them to be
managed without recommending re-excision. Barth
et al. concluded that resection with tumor-free mar-
gins combined with adjuvant radiotherapy is an effec-
tive way to achieve local control in borderline and
MPTB (2).
Many authors feel that in MPTB treated with
BCS or total mastectomy with tumor-free margins
<1 cm, adjuvant irradiation is indicated (1–3,
7–9,21,28,33,34,37). We share this opinion; in our
group, all 6 BCS patients with tumor-free margins
<1 cm underwent adjuvant radiotherapy, and no
local recurrence was seen during 5-years follow-up.
In contrast, most authors state that adjuvant irradia-
tion is not justified in patients with tumor-free mar-
gins ≥1 cm (3,7,8,37). These results are consistent
with our findings; in the analyzed series of 64
patients (34 who underwent total mastectomy and
30 who underwent BCS) with tumor-free margins
≥1 cm, only surgical treatment was performed and
no local recurrence was observed during 5 years fol-
low-up.
Our data supports the opinion that tumor-free
resection margins ≥1 cm in MPTB patients treated
with BCS (or mastectomy, if necessary) is the treat-
ment of choice. If tumor-free margins <1 cm are
reported, adjuvant radiotherapy should be discussed.
FUNDING
None declared.
CONFLICTS OF INTEREST
None declared.
Malignant Phyllodes Tumor of the Breast • 5
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