Breast Cancer (2011) 18:165173

DOI 10.1007/s12282-011-0254-9

SPECIAL FEATURE

Imaging findings of triple-negative breast cancer

Current strategy for triple-negative breast cancer: appropriate

combination of surgery, radiation, and chemotherapy
Hiroshi Yagata Yuka Kajiura Hideko Yamauchi

Received: 21 December 2010 / Accepted: 28 December 2010 / Published online: 3 February 2011
The Japanese Breast Cancer Society 2011

Abstract Triple-negative breast cancer (TNBC) often

grows rapidly and has poor outcomes, with a high recurrence rate and a short interval between recurrence and
death. New molecular-targeted therapies are being developed, but cannot be used at present. Other strategies for the
management of TNBC are needed. TNBC is characterized
by an expanding growth pattern without extensive intraductal spread and is a good candidate for breast-conserving
therapy (BCT) with sufficient margins. The local recurrence rate after BCT is not high as those of other subtypes
of breast cancer. In contrast, the regional recurrence rate is
higher in TNBC than in other subtypes. Sentinel node
biopsy and axillary resection should therefore be performed with the upmost caution. Radiation therapy has
been shown to be useful for the management of TNBC.
Radiation therapy of the chest wall after mastectomy and
the regional area as well as the breast after breast-conserving surgery should be considered. Chemotherapy is the
only systemic treatment available for TNBC. In our hospital, a combination of cyclophosphamide, epirubicin, and
5-fluorouracil (FEC) followed by docetaxel (DTX) or DTX
followed by FEC has been used to treat tumors more than
2 cm in diameter or node-positive breast cancer. Neoadjuvant chemotherapy with these regimens has produced
pathological complete response (pCR) rates higher than
20% in patients with TNBC, regardless of the specific
order of agents. Tumors tend to shrink towards their center
and can be a good indication for BCT. After 3 years, a pCR
is associated with good outcomes, whereas a non-pCR

H. Yagata (&)
Y. Kajiura
H. Yamauchi

Department of Breast Surgical Oncology,
St. Lukes International Hospital, 9-1 Akashi-cho,
Chuo-ku, Tokyo 104-8560, Japan
e-mail: yagata@mvh.biglobe.ne.jp

sometimes results in distant recurrence, even when residual

tumor is minimal. Patients should be closely observed
during neoadjuvant chemotherapy. If there is any evidence
of tumor progression, the chemotherapeutic regimen
should be modified or surgery performed, without losing
the opportunity to administer potentially effective treatment. Several studies indicate that neoadjuvant chemotherapy with platinum-based regimens is effective for
TNBC and is thus an important treatment option. We have
used regimens combining epirubicin and cyclophosphamide (EC) to treat tumors 12 cm in diameter without node
metastasis, and 2 of 21 patients presented with distant
metastases (disease-free interval, 2 and 5 years). We have
not used systemic therapy to treat tumors 1 cm or less in
diameter without node metastasis, and all 8 patients are
alive without recurrence for more than 4 years. After distant recurrence in patients with TNBC, the same chemotherapeutic agents as those used for other subtypes of
breast cancer are recommended, but the response is often
disappointing, leading to poor outcomes. TNBC presents
with different clinical features from other subtypes. The
treatment strategy should be selected according to the
characteristics of the specific subtype of breast cancer.
Keywords Triple-negative breast cancer
Surgery

Radiation
Chemotherapy

Introduction
In Japan, the incidence of breast cancer has been increasing
annually, accompanied by a rise in breast-cancer-related
mortality. In contrast, breast-cancer-related mortality has
been decreasing in the USA because of factors such as
early detection, the use of aggressive systemic therapy, and

123

166

Breast Cancer (2011) 18:165173

improved chemotherapeutic agents [1]. Recently, breast

cancer has been classified in greater detail, and treatment is
selected in accordance with the specific subtype, moving
closer to the goal of tailor-made therapy. Treatment
strategies for breast cancer are no longer similar for different subtypes. Triple-negative breast cancer (TNBC)
refers to breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth
factor receptor 2 (HER2). TNBC usually responds poorly
to endocrine therapy and HER2-targeted therapy and often
grows rapidly, resulting in poor outcomes. New moleculartargeted agents are now being developed, but cannot be
used in general clinical practice. At present, surgery,
radiation, and chemotherapy are the only treatments
available. In this paper, we review and discuss current
effective strategies for the treatment for TNBC on the basis
of our studies and those of others.

Local therapy
The best method for locally controlling TNBC is surgical
excision, similar to other types of breast cancer. TNBC is
usually a unifocal mass lesion with a smooth margin on
magnetic resonance imaging [2], making it a good candidate for breast-conserving therapy (BCT) with negative
resection margins. The risks of local and regional recurrence have been reviewed in several reports (Table 1)
[38]. Nguyen et al. [3] reported that the local recurrence
rate of TNBC was higher than those of hormone-receptorpositive and HER2-negative subtypes, whereas others have
shown that the recurrence rate of TNBC is not higher than
that of non-TNBC or non-basal subtypes [7, 8]. In contrast,
regional or locoregional recurrence is higher in TNBC than
in other subtypes. Although the impact of local or regional
recurrence on outcomes remains unclear, such recurrence
dramatically affects patients quality of life. Therefore,
every effort should be made to avoid false-negative diagnoses on sentinel node biopsy and residual disease on
axillary dissection.

How effective is radiation therapy for local control?

Kyndi et al. [9] reported that radiation therapy decreased
local recurrence after mastectomy in TNBC. Voduc et al.
[8] reported that radiation therapy decreased local recurrence only marginally, but reduced regional recurrence
significantly on multivariate analysis. These findings suggest
that radiation therapy of the chest wall after mastectomy (if
indicated) and of the breast and surrounding region after
breast-conserving surgery should be considered.

Systemic therapy
Anthracyclines and/or taxanes
Chemotherapy is the only systemic therapy for TNBC. The
Japan Breast Cancer Society evidence-based medicine
(EBM) guidelines for drug therapy recommend anthracycline- or taxane-based regimens, or both, as standard chemotherapy for TNBC [10].
Liedtke et al. [11] retrospectively evaluated the effectiveness of neoadjuvant chemotherapy for TNBC. They
reported that the pathological complete response (pCR)
rate was 20% for anthracyclines, 28% for anthracyclines
and taxanes, 12% for taxanes, and 14% for other regimens
and concluded that an anthracycline plus a taxane is the
most effective regimen for TNBC. Patients with TNBC
who had a pCR had good survival and a favorable clinical
course, similar to patients with non-TNBC who had a pCR.
The risk of recurrence was high in the first 3 years after
primary treatment.
FECDTX
In Japan, a phase 2 trial of neoadjuvant chemotherapy with a
combination of fluorouracil, epirubicin, and cyclophosphamide, followed by docetaxel (FECDTX) has been carried
out (JBCRG02) [12]. Patients received four cycles of FEC
(fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2, once every 3 weeks), followed by

Table 1 Local and/or regional recurrence after BCT

LR

RR or LRR

Haffty et al. [4]

TNBC versus non-TNBC

NS

Increase

Nguyen et al. [3]

HR-/HER2- versus HR?/HER2-

Increase

Freedman et al. [5]

TNBC versus non-TNBC

Increase

Millar et al. [6]

Basal versus non-basal

NS

Increase (versus luminal A)

Solin et al. [7]

TNBC versus non-TNBC

NS

Voduc et al. [8]

Basal versus non-basal

NS

Increase

LR local recurrence, RR regional recurrence, LRR locoregional recurrence, HR hormone receptor, NS not significant

123

Breast Cancer (2011) 18:165173

Table 2 Reasons why
FECDTX was not completed
in our patients

167

Chemotherapy

Number of cycles

Outcome

DTX was not given because of CR to FEC

pCR

FEC, then DTX 1 cycle

Interstitial pneumonia

No change or increase by FEC 13 cycles

Increase by DTX 1 cycle

Increase by DTX 3 cycles
Stopped chemotherapy
because of vomiting

DTX docetaxel, pCR

pathological complete response

Decrease by FEC

Increase by DTX 3 cycles

Fig. 1 Distant disease-free survival and overall survival after neoadjuvant chemotherapy (FEC followed by docetaxel) in TNBC

four cycles of docetaxel (75 mg/m2, once every 3 weeks).

The quasi-pCR rate was 25% (16% complete disappearance
of invasive carcinoma in the breast). Hormone-receptornegative and HER2-negative subtypes had quasi-pCR rates
of 35%. In our hospital, we have also used FECDTX as a
standard regimen for stage 2 or 3 breast cancer.
Between January 2004 and December 2007, we gave
neoadjuvant chemotherapy with FECDTX to 58 patients
in whom TNBC was diagnosed on core needle biopsy
[estrogen receptor negative, progesterone receptor negative, and HER2 expression of 0 or 1 or HER2 expression of
2 plus fluorescence in situ hybridization (FISH) negative].
The disease stage was 2 or 3 on the basis of radiologic
findings. Patients who had a diagnosis of non-TNBC on
final pathological examination were excluded. Median age
was 53.5 years (range 3169), and median follow-up was
46 months (range 1174). The rate of pCR, defined as no
invasive cancer in the breast or axillary samples, was
22.4% (13 of 58 patients). Eight patients did not complete
FECDTX (Table 2). Three patients did not receive DTX
because of clinical complete responses on magnetic resonance imaging and ultrasonography after 4 cycles of FEC.

All of these patients had pCR on final pathological examination. One patient could not continue chemotherapy
because of interstitial pneumonia after one cycle of DTX.
Three patients did not respond to one to three cycles of
FEC. Two of these patients also did not respond to one or
three cycles of DTX, and the other refused to continue
chemotherapy because of severe nausea and vomiting. One
patient did not receive the fourth cycle of DTX because of
a slight increase in tumor size after 3 cycles of DTX,
despite a good response to FEC. Distant disease-free survival was 74.1%, and overall survival was 81.0% (Fig. 1).
All distant metastases developed within 3 years, and 10
(91%) of the 11 patients with distant metastases died within
3 years, showing that the interval between the start of
chemotherapy and the development of distant metastases is
short, as is subsequent survival. Distant metastases were
not apparent in patients with pCR (Fig. 2). On pathological
examination, invasive cancers became 1.0 cm or less in
diameter and node negative after neoadjuvant chemotherapy in 10 patients. Two patients had distant metastases,
leading to death. These findings suggest that chemotherapy
may not sufficiently improve outcomes in patients without

123

168

Breast Cancer (2011) 18:165173

Fig. 2 Distant disease-free survival and overall survival of patients with pCR and those with non-pCR after neoadjuvant chemotherapy (FEC
followed by docetaxel) in TNBC

pCR, even if tumors shrink. Further studies are needed to

evaluate prognostic and predictive factors in non-pCR
patients.
In 13 patients (22.4%), tumors were unchanged or grew
slightly in response to FEC. Distant metastases developed
in 7 (53.8%) of these patients, resulting in death. In only 1
patient, the tumor shrank dramatically and reached a pCR.
The patient is alive without any recurrence. The tumor
increased in diameter, but central necrosis developed in
response to FEC, suggesting that FEC was effective
(Fig. 3). Nine patients (15.5%) had tumor regrowth during
DTX after shrinkage in response to FEC, but tumor
regrowth was not detected until the completion of 4 cycles
of DTX in 8 of these patients. DTX treatment was thus of
no benefit in most of these patients with FEC-responsive
tumors.
Breast-conserving therapy was performed after FEC
DTX in 42 patients (72.4%). Two patients (4.8%) had local
recurrence, but were alive without distant metastasis. Total
mastectomy was performed in 16 patients. One patient had
local recurrence, but is still alive without distant metastasis.
Three patients (5.6%) had regional recurrence, and 1 had
brain metastasis. Thus, BCT is an important option for
surgical treatment, even after neoadjuvant chemotherapy
for TNBC.

Fig. 3 The response was evaluated as progressive disease after FEC,

but the center of the tumor appeared to have undergone necrosis

DTXFEC
Neoadjuvant therapy with DTX followed by FEC (DTX
FEC) produced a pCR rate of 23% (including near pCR,
29%) in the JBCRG03 trial [13]. The efficacy of DTX
FEC in the JBCRG03 trial was thus not inferior to that of
FECDTX in the JBCRG02 trial.

123

In our hospital, DTXFEC has been used as a standard

regimen since 2008. From March 2008 through December
2009, DTXFEC was given to 21 patients with TNBC.
The rate of pCR, defined as no invasive cancer in the
breast, was 28.6% (6 patients) as compared with 24.1% for

Breast Cancer (2011) 18:165173

169

Table 3 Neoadjuvant chemotherapy with platinum-based regimens for TNBC

References

Regimen

pCR rate (%)

Hurley et al. [14]

w-DTX (35 mg/m2)/w-CBDCA (AUC 2) q4w (day 1, 8, 15) 9 4

22

Sikov et al. [15]

w-PTX (80 mg/m2)/4w-CBDCA (AUC 6) 9 4

67

Chen et al. [16]

w-PTX (80 mg/m2)/w-CBDCA (AUC 2) q4w (day 1, 8, 15) 9 4

33.3

Silver et al. [17]

3w-CDDP (75 mg/m ) 9 4

Byrski et al. [18]

3w-CDDP (75 mg/m2) 9 4

Frasci et al. [19]

22
83a
2

w-CDDP (30 mg/m )/w-EPI (50 mg/m )/w-PTX (50 mg/m ) with G-CSF 9 8

62

DTX docetaxel, CBDCA carboplatin, PTX paclitaxel, CDDP cisplatin, EPI epirubicin, AUC area under the curve, w weekly, 3w triweekly, q4w
every 4 weeks
a

Young women with BRCA1-positive breast cancer

FECDTX. DTXFEC was considered equivalent to or

more effective than FECDTX. Tumors remained
unchanged or grew slightly in 7 patients (33.3%) in
response to DTX, which was withdrawn after 1 or 2 cycles
and switched to FEC in 5 patients. Six of the 7 patients
with no response or progressive disease showed various
degrees of response to FEC. Only one patient had tumor
reduction during DTX, but regrowth during FEC.
Because DTX has more unresponsive tumors than FEC
and few tumors that respond at least slightly to DTX show
regrowth during FEC, the most rational approach seems to
be to start treatment with DTX and evaluate the response to
the first or second cycle of DTX. If ineffective, DTX
should be promptly discontinued and switched to FEC.
This order of treatment is expected to reduce the risk of
administering ineffective treatment.
Platinum-based regimens
Recently, several studies have evaluated the effectiveness
of platinum-based regimens for TNBC (Table 3) [1419].
Hurley et al. [14] reported a pCR rate of 22% for a combination of weekly docetaxel and weekly carboplatin.
Subsequently, Sikov et al. [15] obtained an amazing pCR
rate of 67% with a combination of weekly paclitaxel plus
carboplatin every 4 weeks, although it is unclear whether
the good results were due to the regimen or selection bias
of the participants. Byrski et al. [18] reported that triweekly
cisplatin produced a pCR rate 83% in young women
with BRCA1-positive breast cancer. Frasci et al. [19] gave
patients with TNBC intensive neoadjuvant chemotherapy
with a combination of cisplatin, epirubicin, paclitaxel
plus granulocyte-colony stimulating factor (G-CSF) and
achieved a pCR rate of 62%. Platinum-based chemotherapy
has thus been shown to be effective for TNBC and should
be considered as an option for neoadjuvant chemotherapy.
In particular, such therapy is expected to be very effective
in BRCA1 carriers and may be effective in patients who do
not adequately respond to anthracycline- and taxane-based
regimens.

Stage 1 TNBC
The optimal treatment for stage 1 TNBC remains controversial. The National Comprehensive Cancer Network (NCCN)
guidelines propose that chemotherapy is indicated for TNBC
[20]. These guidelines recommend chemotherapy for tumors
exceeding 1 cm in diameter and propose that chemotherapy
should be considered for tumors 1 cm or less in diameter.
In our hospital, we performed breast surgery in 29
patients with pathological stage 1 TNBC (microinvasion
excluded) between January 2003 and December 2006.
Median follow-up was 60 months (range 3489). Twentyone patients had pathological T1c disease, and 20 underwent BCT with sentinel lymph-node biopsy. They received
4 cycles of epirubicin (90 mg/m2) plus cyclophosphamide
(500 mg/m2) every 3 weeks (EC). One patient had liver
metastasis 61 months after surgery, and another had local
and regional recurrence 37 months after surgery, followed
by lung metastasis. They had better outcomes than patients
with stage 2 or 3 disease, and metastasis developed after
3 years or longer, but the effectiveness of the EC regimen
is unclear. Eight patients had pathological T1a-b disease,
received no adjuvant chemotherapy, and had no evidence
of recurrence for more than 4 years.
Our results suggest that aggressive chemotherapy cannot
currently be recommended for the management of tumors
1 cm or less in diameter. The association between chemotherapy and the impact on outcomes should be validated
by clinical trials in women with stage 1 TNBC.

Distant metastasis from TNBC

TNBC or basal-like tumors have characteristic sites of
distant metastasis as compared with non-TNBC or nonbasal tumors. Lin et al. [21] of the Dana-Farber Cancer
Institute reported that 75% of distant metastases from
TNBC occurred in 3 years and that overall survival after
distant metastasis was 13.3 months. The most common
metastatic sites were the lung (41%), liver (29%), bone

123

170

Breast Cancer (2011) 18:165173

(24%), and central nervous system (CNS; 46%). The CNS

was the first site of metastases in 14% of patients. CNS
metastases were usually accompanied by metastases in
other sites. Luck et al. [22] compared metastatic patterns
between basal-type and non-basal-type breast cancer at
Nottingham City Hospital. The first metastatic sites were
the lung (basal type 52% vs. non-basal type 23%), CNS (18
vs. 2%), and bone (23 vs. 47%). Median survival of
patients with metastatic disease was 10.1 months for basal
type (vs. 25 months for non-basal type). Kennecke et al.
studied the characteristics of metastases according to subtype. Median survival with distant metastasis was 2.2 years
for luminal A breast cancer, 1.6 years for luminal B,
1.3 years for luminal/HER2, 0.7 years for HER2 enriched,
and 0.5 years for basal-like, which had the shortest survival
[23]. The most common metastatic sites in basal-like breast
cancer were the CNS, lung, and distant nodes, whereas
liver and bone metastases were less common, albeit bone is
usually the most frequent site of recurrence in breast cancer. Kassam et al. [24] reported that the duration of chemotherapy after recurrence was short: 11.9 weeks for first
line, 9 weeks for second line, and 4 weeks for third line.
In our hospital, 15 (25.9%) of 58 patients had distant
metastases after neoadjuvant chemotherapy with FECDTX
as described above (Table 4). Lung and bone were the most
common first sites of metastases, but most cases of metastases
involved multiple organs. Metastases to the CNS developed in
5 patients (33.3%) as first metastases and in 9 patients (60%)
overall. Our findings suggest that when metastases are suspected, multiple organs including the CNS should be carefully
examined to detect any distant metastasis. Overall survival
after distant metastasis was short (median 6.4 months; range
027.1 months), indicating that outcomes after distant
metastasis were very poor (Fig. 4). After the development of
metastasis, the effect of standard chemotherapy for breast
cancer was generally very limited, resulting in early deterioration of general condition due to rapid tumor growth. Recent
data on neoadjuvant chemotherapy with platinum-based regimens suggest that the early use of platinum after the onset of
metastasis might improve outcomes in TNBC.
Table 4 Distant metastases after neoadjuvant
(FECDTX) at St. Lukes International Hospital
Number
(rate %)

Number of first
recurrences only
at single site

Lung

7 (46.7)

Bone

7 (46.7)

Non-regional lymph nodes

4 (26.7)

Liver

3 (20.0)

CNS

5 (33.3)

123

Some TNBC tumors grow very rapidly. Early detection and

prompt treatment of such tumors and any recurrence are
essential. Otherwise, the opportunity for appropriate treatment and sufficient tumor control will be lost. In TNBC,
prognostic markers such as histological grade or nuclear
grade do not provide a firm basis for predicting tumor
growth. Even MIB-1 index is of limited value as a measure
of the speed of tumor growth. Tumors with a very high
mitotic count or a nuclear grade estimated to be higher than
3 (currently the highest grade) require special attention.

Case presentation
A 30-year-old premenopausal woman without a family
history of breast cancer or ovarian cancer was given a
diagnosis of breast cancer and underwent mastectomy with
level 1 and 2 axillary dissection in another hospital. Pathological examination revealed invasive ductal carcinoma, a
maximum tumor diameter of 3.1 cm, pN1 (3/22), ly0,
nuclear grade 3, estrogen receptor 0, progesterone receptor
0, and HER2 0. She received postoperative chemotherapy
with FECDTX. Rotters lymph node metastasis was
detected after a disease-free interval, 11 months after surgery. Weekly vinorelbine (25 mg/m2 on days 1 and 8,
every 3 weeks) was started, but the lymph nodes continued
to grow during chemotherapy. She was referred to our
hospital for further treatment. Computed tomography
showed Rotters lymph node swelling (Fig. 5). She
underwent removal of Rotters lymph nodes and level 3
lymph nodes for short-term local control because the effect

chemotherapy

Initial site of
recurrence

DTX docetaxel

Special considerations for rapidly growing tumors

Fig. 4 Overall survival after distant recurrence in TNBC (patients

given neoadjuvant chemotherapy)

Breast Cancer (2011) 18:165173

of further chemotherapy was likely to be minimal. Histopathological studies revealed metastatic lymph nodes from
TNBC. The tumor was 6.0 cm in maximum diameter
and nuclear grade 3. The mitotic count was very high
(60 per 10 high-power fields). Radiation to the chest wall
and supraclavicular lymph nodes was given. Cough developed 4 months after lymphadenectomy, and computed

Fig. 5 Rotters lymph nodes were swollen up to 6 cm

171

tomography revealed multiple lung nodules consistent with

the courses of blood vessels, evaluated to be multiple lung
metastases (Fig. 6). Paclitaxel (80 mg/m2) and carboplatin
(AUC 2) were given on days 1, 8, and 15 every 4 weeks, and
the lung nodules disappeared in 2 weeks. Clinically, a
complete response has been maintained for more than
8 months.
What is the treatment of choice on the detection of
Rotters lymph node metastasis? How should locoregional
recurrence be managed? Drug susceptibility should be
checked before starting systemic therapy. Chemotherapy,
radiation therapy, or both might produce a clinical response
and local control, but it is difficult to predict response.
TNBC can grow rapidly within a short time and is often
resistant to standard chemotherapy. The opportunity for
local control by surgery may thus be lost. Preferably, local
control by surgery, radiation, or both should be performed
first and then chemotherapy should be considered in
patients with TNBC. Initiating treatment with chemotherapy could be cautiously considered if the tumor is growing

Fig. 6 Multiple lung

metastases appeared

123

172

slowly and can be expected to respond to anticancer agents.

Progression of local disease negatively affects patients
quality of life, and local control has a high priority, irrespective of the impact on survival.
Which regimen of chemotherapy should be used to treat
patients with lung metastases? Anthracyclines, taxanes,
and vinorelbine are ineffective, and other standard regimens of chemotherapy are unlikely to be beneficial. Platinum compounds might be worth trying in patients with
TNBC with no response to standard regimens.

Summary
Our findings and the results of previous studies of TNBC
are summarized as follows: BCT is an important option for
local therapy and can be performed after neoadjuvant
chemotherapy. Radiotherapy also has an important role in
local control after surgery. Recurrence tends to occur early
after surgery, followed by rapid disease progression,
leading to poor outcomes. Anthracycline- and taxane-based
regimens achieve high pCR rates, resulting in excellent
outcomes. In contrast, patients with a non-pCR have a high
risk of recurrence and require alternative treatment strategies. In patients who receive FECDTX, no response to
FEC is associated with a poor prognosis, and subsequent
treatment with DTX is of limited effectiveness. With the
FECDTX regimen, regrowth of tumors that markedly
shrink during treatment with FEC is difficult to detect after
switching to DTX. DTXFEC regimens can achieve pCR
rates comparable to those with FECDTX and are therefore
useful options for neoadjuvant chemotherapy. In patients
given DTXFEC regimens, few tumors that respond well
to DTX show regrowth during treatment with FEC.
Therefore, in patients who respond to DTX, subsequent
treatment with FEC can be continued with relative confidence. When DTX is ineffective, it is difficult to predict the
impact of subsequent FEC on outcomes. Many recurrent
tumors are resistant to standard chemotherapy for breast
cancer. Platinum-containing regimens should be considered as an important treatment option for TNBC in both
neoadjuvant and metastatic settings. In patients with stage
1 TNBC, pathological T1a-b tumors have good prognoses
without chemotherapy, and pT1c tumors also have a
favorable prognosis after adjuvant chemotherapy (4 cycles
of EC). The CNS is a common site of distant metastasis,
and radiologic examinations should be performed carefully
in patients with TNBC who develop metastases of the other
sites. Local therapy should be considered for locoregional
recurrence before the opportunity for treatment is lost.
In conclusion, TNBC should be treated with an appropriate combination of surgery, radiation therapy, and

123

Breast Cancer (2011) 18:165173

chemotherapy. It is expected that more effective agents for

TNBC will become available in the near future.

References
1. Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi
GN. Is breast cancer survival improving? Cancer. 2004;100:4452.
2. Uematsu T, Kasami M, Yuen S. Triple-negative breast cancer:
correlation between MR imaging and pathologic findings. Radiology. 2009;250:63847.
3. Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF,
Boon WL, et al. Breast cancer subtype approximated by estrogen
receptor, progesterone receptor, and HER-2 is associated with
local and distant recurrence after breast-conserving therapy.
J Clin Oncol. 2008;26:23738.
4. Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas
J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin
Oncol. 2006;24:56527.
5. Freedman GM, Anderson PR, Li T, Nicolaou N. Locoregional
recurrence of triple-negative breast cancer after breast-conserving
surgery and radiation. Cancer. 2009;115:94651.
6. Millar EK, Graham PH, OToole SA, McNeil CM, Browne L,
Morey AL, et al. Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage
invasive breast cancer using a five-biomarker panel. J Clin Oncol.
2009;27:47018.
7. Solin LJ, Hwang WT, Vapiwala N. Outcome after breast conservation treatment with radiation for women with triple-negative
early-stage invasive breast carcinoma. Clin Breast Cancer.
2009;9:96100.
8. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO,
Kennecke H. Breast cancer subtypes and the risk of local and
regional relapse. J Clin Oncol. 2010;28:168491.
9. Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM,
Overgaard J. Estrogen receptor, progesterone receptor, HER-2,
and response to postmastectomy radiotherapy in high-risk breast
cancer: the Danish Breast Cancer Cooperative Group. J Clin
Oncol. 2008;26:141926.
10. Japan Breast Cancer Society. EBM guideline for drug therapy.
2nd ed. Tokyo: Kanehara; 2010. p. 1079.
11. Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA,
et al. Response to neoadjuvant therapy and long-term survival in
patients with triple-negative breast cancer. J Clin Oncol.
2008;26:127581.
12. Toi M, Nakamura S, Kuroi K, Iwata H, Ohno S, Masuda N, et al.
Phase II study of preoperative sequential FEC and docetaxel
predicts of pathological response and disease free survival. Breast
Cancer Res Treat. 2008;110:5319.
13. Sato N, Iwata H, Masuda N, Nakamura S, Yamamoto N, Kuroi K,
et al. Neoadjuvant docetaxel (DTX 75) followed by fluorouracil,
epirubicin, cyclophosphamide (FEC 100) in primary operable
breast cancer: results of a multicenter phase II trial: JBCRG03
trial. Proceedings of the 6th European Breast Cancer conference;
2008 1519 Apr; Berlin, Germany (abstract 245).
14. Hurley J, Reis I, Silva O, Gomez C, DeZarraga F, Velez P, et al.
Weekly docetaxel/carboplatin as primary systemic therapy for
HER2-negative locally advanced breast cancer. Clin Breast
Cancer. 2005;5:44754.
15. Sikov WM, Dizon DS, Strenger R, Legare RD, Theall KP, Graves
TA, et al. Frequent pathologic complete responses in aggressive
stages II to III breast cancers with every-4-week carboplatin and

Breast Cancer (2011) 18:165173

16.

17.

18.

19.

weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. J Clin Oncol. 2009;27:4693700.
Chen XS, Nie XQ, Chen CM, Wu JY, Wu J, Lu JS, et al. Weekly
paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer.
Ann Oncol. 2010;21:9617.
Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li
Q, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast
cancer. J Clin Oncol. 2010;28:114553.
Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M,
Stawicka M, et al. Pathologic complete response rates in young
women with BRCA1-positive breast cancers after neoadjuvant
chemotherapy. J Clin Oncol. 2010;28:3759.
Frasci G, Comella P, Rinaldo M, Iodice G, Di Bonito M, DAiuto
M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with
G-CSF support in triple-negative large operable breast cancer.
Ann Oncol. 2009;20:118592.

173
20. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology version 3: breast cancer. 2010.
http://www.nccn.org. Accessed 20 Dec 2010.
21. Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP. Sites
of distant recurrence and clinical outcomes in patients with
metastatic triple-negative breast cancer: high incidence of central
nervous system metastases. Cancer. 2008;113:263845.
22. Luck AA, Evans AJ, Green AR, Rakha EA, Paish C, Ellis IO. The
influence of basal phenotype on the metastatic pattern of breast
cancer. Clin Oncol (R Coll Radiol). 2008;20:405.
23. Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D,
Speers CH, et al. Metastatic behavior of breast cancer subtypes.
J Clin Oncol. 2010;28:32717.
24. Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C,
et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial
design. Clin Breast Cancer. 2009;9:2933.

123