Beruflich Dokumente
Kultur Dokumente
DOI 10.1245/s10434-014-4122-7
ABSTRACT
Background. The impact of tumor focality on type of
surgery, local recurrence rate, and survival after neoadjuvant chemotherapy (NACT) for breast cancer is not fully
understood. This study aimed to compare local recurrencefree survival (LRFS), disease-free survival (DFS), and
overall survival (OS) according to focality stratified by
type of surgery and pathologic complete response (pCR),
with a focus on breast conservation.
Methods. Participants (n = 6,134) in the GeparTrio, GeparQuattro, and GeparQuinto trials with operable or locally
advanced tumors receiving NACT were classified as having unifocal (1 lesion), multifocal (C2 lesions in 1
quadrant), or multicentric (C1 lesion in C2 quadrants)
disease. The study investigated LRFS, DFS, and OS
according to focality stratified by type of surgery and
pathologic complete response.
Results. The patients were classified as having unifocal
(n = 4,733, 77.1 %), multifocal (n = 820, 13.4 %), or
multicentric (n = 581, 9.5 %) tumors. The respective pCR
Electronic supplementary material The online version of this
article (doi:10.1245/s10434-014-4122-7) contains supplementary
material, which is available to authorized users.
Society of Surgical Oncology 2014
First Received: 11 June 2014;
Published Online: 9 October 2014
B. Ataseven, MD
e-mail: ataseven@gmx.net
1119
b
1.0
0.8
0.6
0.4
log-rank p = 0.002
0.2
1.0
0.8
0.6
0.4
log-rank p = 0.030
0.2
Single
Multifocal
Multicentric
0
10
No. at risk
Single
4733
Multifocal
820
Multicentric 581
3250
580
389
1807
274
199
601
89
58
Single
Multifocal
Multicentric
57
9
8
0
0
0
Single
4276
Multifocal
822
Multicentric 381
841
219
253
450
109
117
127
38
31
9
6
4
0
0
0
0.8
0.6
0.4
log-rank p = 0.003
0.2
1.0
0.8
0.6
0.4
log-rank p = 0.314
0.2
Single
Multifocal
Multicentric
0
Single
3759
668
Multifocal
Multicentric 487
2576
472
321
1426
227
164
474
76
51
48
7
7
0
0
0
1.0
0.8
0.6
0.4
log-rank p = 0.724
Single
Multifocal
Multicentric
0
No. at risk
Single
907
132
Multifocal
Multicentric 82
10
378
47
34
126
13
7
9
2
1
0
No. at risk
0.2
Single
Multifocal
Multicentric
10
No. at risk
10
1.0
No. at risk
0
0
0
Single
3217
454
Multifocal
Multicentric 163
10
1329
155
77
463
48
24
47
2
3
0
0
1120
b FIG. 1 Local relapse-free-survival according to unifocal, multifo-
B. Ataseven et al.
Treatment
The participants in the GeparTrio study received two
cycles of docetaxel/doxorubicin/cyclophosphamide (TAC).
The patients with an early response were randomized to
four or six further TAC cycles. The patients without an
early response were randomized to four further cycles of
TAC or four cycles of vinorelbine/capecitabine. AntiHER2-therapy was not applied. The participants in the
GeparQuattro study initially received four cycles of epirubicin/cyclophosphamide and then were randomized to one
of the three arms for four cycles of docetaxel, four cycles
of docetaxel/capecitabine, or four cycles of docetaxel
respectively followed by four cycles of capecitabine. For
cases of HER2? disease, trastuzumab was administered for
a total of 1 year, starting with the first neoadjuvant treatment cycle. A similar chemotherapy was administered to
the GeparQuinto participants. However, the patients with
HER2? tumors randomly received either trastuzumab or
lapatinib, and the patients with HER tumors randomly
received bevacizumab or no bevacizumab concomitant to
all chemotherapy cycles. The patients without response to
the first four chemotherapy cycles with or without bevacizumab were randomized to either weekly paclitaxel or
weekly paclitaxel with everolimus. Treatment was discontinued, and further treatment was administered at the
discretion of the investigator in case of local tumor progression during chemotherapy.
All the patients were allocated to surgery after the end of
neoadjuvant chemotherapy. The type of surgery (breast
conservation or mastectomy) was left to the investigators
discretion. In case of breast conservation, a tumor-free
margin was warranted. The recommended postoperative
treatment consisted of radiotherapy to the ipsilateral
remaining breast for patients treated by breast conservation
and radiotherapy to the chest wall with or without regional
nodes in case of mastectomy for patients with an initial
tumor larger than 5 cm or clinically positive suspect axillary nodes before treatment or at least one histologically
involved node after neoadjuvant treatment. Endocrine
treatment for 5 years after surgery was recommended for
patients with hormone-receptor-positive tumors. Detailed
information about actual accomplished adjuvant treatment
and duration was not available. Therefore, adjuvant treatment was not included as a variable in the multivariate
analysis. The patients were followed up according to local
guidelines. Detailed methods and results of the studies have
been published recently.1519 All the patients consented to
participate in the study, and all the necessary authority
approvals were obtained for performance of the clinical
trials and for further use of anonymized data in subsequent
research projects.
1121
Unifocal
%
Multifocal
Multicentric
P Value
(uni- vs. multifocal)
P Value
(uni- vs. multicentric)
Age (years)
\35
384
6.3
296
6.3
53
6.5
35
6.0
3539
4049
603
2,165
9.8
35.3
450
1,654
9.5
34.9
92
301
11.2
36.7
61
210
10.5
36.1
5059
1,779
29.0
1,386
29.3
232
28.3
161
27.7
[60
1,203
19.6
947
20.0
142
17.3
114
19.6
Total
6,134
4,733
820
0.233
0.868
\0.001
\0.001
0.015
\0.001
0.276
0.077
0.088
0.140
0.003
0.048
0.014
0.001
0.004
\0.001
581
497
8.1
341
cT2
cT3
7.2
105
12.9
51
8.8
3,767
61.5
3,009
63.7
492
60.2
266
46.1
992
16.2
756
16.0
123
15.1
113
19.6
cT4ac
449
7.3
333
7.0
55
6.7
61
10.6
cT4d
416
6.8
288
6.1
42
5.1
86
14.9
Total
6,121
4,727
817
577
2,831
46.6
2,285
48.8
352
43.0
194
33.7
cN1
2,928
48.2
2,186
46.7
420
51.3
322
56.0
cN2
cN3
242
72
4.0
1.2
167
42
3.6
0.9
35
11
4.3
1.3
40
19
7.0
3.3
Total
6,073
4,680
818
575
Histologic type
Ductal-invasive
Lobular-invasive
Other invasive
Total
5,011
81.8
3,865
81.7
681
83.3
465
80.0
673
11.0
506
10.7
88
10.8
79
13.6
444
7.2
358
7.6
49
6.0
37
6.4
6,128
4,729
818
581
Grading
G1
209
3.5
161
G2
3,284
55.2
2,496
3,5
54.3
G3
2,457
41.3
1,943
42.2
Total
5,950
4,600
30
3.8
18
460
58.2
328
58.7
301
38.1
213
38.1
791
3,2
559
2,144
35.4
1,706
36.5
254
31.1
184
32.3
HR?
3,916
64.6
2,968
63.5
562
68.9
386
67.7
Total
HER2 status
6,060
4,674
816
Negative
4,165
72.9
3,258
74.1
542
69.9
365
67.2
Positive
1,547
27.1
1,136
25.9
299
30.1
178
32.8
Total
5,712
4,394
570
775
543
Intrinsic subtype
Luminal A
2,011
35.7
1,522
35.1
287
37.5
202
38.1
Luminal B
707
12.6
555
12.8
92
12.0
60
11.3
Luminal HER2?
895
15.9
660
15.2
142
18.6
93
17.5
Nonluminal HER2?
637
11.3
466
10.7
89
11.6
82
15.5
TNBC
1,382
24.5
1,134
26.1
155
20.5
93
17.5
Total
5,632
4,337
765
530
1122
B. Ataseven et al.
TABLE 1 continued
Total
n
Unifocal
%
Multifocal
Multicentric
P Value
(uni- vs. multifocal)
P Value
(uni- vs. multicentric)
\0.001
\0.001
0.050
0.004
Type of surgery
Breast conservation
3,834
66.0
3,217
71.6
454
58.5
163
30.0
Mastectomy
1,979
34.0
1,276
28.4
322
41.5
381
70.0
Total
5,813
Pathologic complete response
4,493
776
544
No
4,914
81.4
3,759
80.6
668
83.5
487
85.6
Yes
1,121
18.6
907
19.4
132
16.5
82
14.4
6,035
4,666
800
569
Statistical Analysis
Statistical analysis was performed using SPSS software
version 20.0 (SPSS Inc. Chicago, IL, USA). Correlation
between focality and the clinicopathologic parameters was
assessed by v2 testing. Uni- and multivariate Cox regression analyses were conducted to identify factors predicting
survival. The analyses were conducted according to intentto-treat principles and adjusted for age, cT-stage, cN-stage,
histologic type, grading, hormone receptor and HER2-status, type of surgery, and pathologic complete response.
Survival was plotted by KaplanMeier curves, and differences between groups were analyzed using the log-rank
test. All the tests were two-sided, with significance levels
set at 0.05 without correction for multiple testing.
Clinicopathologic Characteristics
The univariate analysis and log-rank test results concerning the survival end points for all the focality groups
are provided overall and by type of surgery or achievement
of pathologic complete response in Table 2. We chose
unifocality as the reference group to identify the impact of
focality on survival.
Local Relapse-Free Survival The 3-year local relapsefree survival rate was 92.9 % for the patients with unifocal
tumor, 95.1 % for the patients with multifocal tumor, and
90.4 % for the patients with multicentric tumor
(P = 0.002) (Fig. 1a). Interestingly, the patients with
multifocal tumors showed fewer local recurrences than
the patients with unifocal tumors (P = 0.031). This effect
was more pronounced among the patients treated with
mastectomy (P = 0.009; Fig. 1b) and those who failed to
achieve a pathologic complete response (P = 0.034;
Fig. 1c). No significant difference between uni- and
multifocality was detected for the patients treated with
breast conservation or the patients with a pathologic
complete response. In general, the patients with
multicentric tumors showed the highest local relapse
rates. However, local recurrence-free survival was not
RESULTS
1123
TABLE 2 Locoregional, overall relapse, and death events for all focality groups by type of surgery or achievement of a pathologic complete
response (ypT0 ypN0)
Local relapse-free survival
Events
Total n
P Value
%
Disease-free survival
a
Events
n
Overall survival
P Value
P Valuea
Events
n
All patients
Unifocal
4,733
336
7.1
886
18.7
Multifocal
820
40
4.9
0.031
133
16.2
0.178
89
10.5
0.735
Multicentric
581
56
9.6
0.015
142
24.4
\0.001
89
15.3
0.009
6,134
432
7.0
0.002
1,161
18.9
\0.001
736
12.0
0.025
Total
558
11.8
Type of surgery
Breast conservation
Unifocal
3,217
182
5.7
463
14.4
274
8.5
Multifocal
454
19
4.2
0.260
60
13.2
0.717
37
8.2
0.916
Multicentric
163
13
8.0
0.347
30
18.4
0.316
18
11.0
0.528
3,834
214
5.6
0.314
553
14.4
0.546
328
8.6
0.820
1,276
140
11.0
375
29.3
246
19.3
322
381
19
41
5.9
10.8
0.009
0.994
64
100
20.0
26.5
0.002
0.444
45
60
14.1
15.9
0.070
0.253
1,979
200
10.1
0.030
539
27.2
0.009
350
17.8
0.137
Total
Mastectomy
Unifocal
Multifocal
Multicentric
Total
907
25
2.8
75
8.3
38
4.2
Multifocal
132
1.5
0.430
5.3
0.290
3.8
0.876
82
2.4
0.844
11
13.4
0.104
8.5
0.081
1,121
29
2.6
0.724
93
8.3
0.121
50
4.5
0.202
514
13.7
Multicentric
Total
3,759
309
8.2
803
21.4
Multifocal
668
38
5.7
0.034
125
18.7
0.192
83
12.4
0.604
Multicentric
487
54
11.1
0.020
129
26.5
0.004
81
16.6
0.055
4,914
401
8.2
0.003
1,057
21.5
0.004
678
13.8
0.114
28
3.7
Total
Pathologic complete response/no pathologic complete response in patients treated by type of surgery
Breast conservation and pathologic complete response
Unifocal
759
20
2.6
Multifocal
86
1.2
Multicentric
30
3.3
875
22
2.5
Total
58
7.6
0.432
5.8
0.609
4.7
0.640
0.965
6.7
0.674
3.3
0.798
0.731
65
7.4
0.811
33
3.8
0.858
403
1.7
246
10.0
2,436
161
6.6
Multifocal
358
18
5.0
0.295
55
1.5
0.690
33
9.2
0.780
Multicentric
131
12
9.2
0.366
28
2.1
0.263
17
13.0
0.526
2,925
191
6.5
0.354
486
16.6
0.471
296
10.1
0.776
16
13.3
10
8.3
Total
120
3.3
37
0.262
2.7
0.093
2.7
0.288
47
204
1
5
2.1
2.5
0.710
0.527
9
26
19.1
12.7
0.209
0.066
6
17
12.8
8.3
0.319
0.254
1124
B. Ataseven et al.
TABLE 2 continued
Local relapse-free survival
Events
Total n
Disease-free survival
P Value
Events
Overall survival
P Value
P Valuea
Events
1,150
136
11.8
358
31.1
235
20.4
281
19
6.8
0.018
63
22.4
0.010
44
15.7
0.142
330
1,761
40
195
12.1
11.1
0.826
0.051
89
510
27.0
29.0
0.268
0.029
53
332
16.1
18.9
0.160
0.173
Multifocal
Multicentric
Total
a
Unifocal tumors are the reference group and are compared with multifocal and multicentric tumors, respectively. The P values in the total
line refer to log-rank tests over all three groups
Luminal B
Event
Total
1,522
60
287
Multicentric
Total
202
2,011
10
77
P Value
0.306
Unifocal
Multifocal
Luminal HER2?
Event
%
Event
Total
3.9
555
31
2.4
92
5.0
3.8
60
707
6
41
10.0
5.8
0.337
Nonluminal HER2?
Event
Total
5.6
660
46
4.3
142
93
895
6
57
6.5
6.4
0.476
TNBC
Total
7.0
466
3.5
89
82
637
0.096
Event
%
Total
42
9.0
1,134
129
11.4
5.6
155
17
11.0
12
59
14.6
9.3
93
1,382
14
160
15.1
11.6
0.386
lower for the patients with multicentric tumors than for the
patients with uni- and multifocal tumors if pathologic
complete response was achieved or breast conservation was
performed (Fig. 1d, e). The local relapse rates for the three
focality groups did not differ between the breast cancer
subtypes (Table 3).
Disease-Free Survival A total of 1,161 patients (18.9 %)
experienced relapse, including 886 patients (18.7 %) in the
unifocal group, 133 patients (16.2 %) in the multifocal
group, and 142 patients (24.4 %) in the multicentric group.
The difference between the patients with unifocal tumors
and those with multifocal tumors was not significant
(P = 0.178). A statistically significant difference was
detected between the patients with unifocal tumors and
those with multicentric tumors (3-year DFS: 81.3 vs.
75.6 %; P \ 0.001; Fig. 2a). The patients with breast
conservation after neoadjuvant chemotherapy (Fig. 2b,
P = 0.316) and those who achieved a pathologic
complete response (Fig. 2c, P = 0.104) showed no
difference in disease-free survival when the diagnosis
was either unifocal or multicentric tumor. In the cohort of
patients who underwent mastectomy, disease-free survival
was significantly better for the patients with multifocal
tumors than for those with unifocal tumors, whereas no
1125
b
1.0
Proportion disease-free
Proportion disease-free
1.0
0.8
0.6
0.4
0.2
0.8
0.6
0.4
log-rank p = 0.546
0.2
Single
Multifocal
Multicentric
0
Single
4733
Multifocal 820
Multicentric 581
3157
560
370
1736
259
183
578
85
55
55
9
8
10
No. at risk
Single
Multifocal
Multicentric
No. at risk
0
0
0
Single
3217
Multifocal
454
Multicentric 163
10
1286
150
72
451
47
22
46
2
3
0
0
0
Proportion disease-free
1.0
0.8
0.6
0.4
log-rank p = 0.121
0.2
Single
Multifocal
Multicentric
0
No. at risk
Single
907
Multifocal 132
Multicentric 82
10
377
47
31
126
13
7
9
2
1
0
0
0
FIG. 2 Disease-free-survival according to unifocal, multifocal, and multicentric breast cancer among a all patients, b breast conservation
patients, and c patients achieving a pathologic complete response
extended operations or mastectomies. Mastectomy is recommended in general for patients with multicentric disease
irrespective of previous neoadjuvant chemotherapy.14 The
data are insufficient to support the use of breast conservation after neoadjuvant chemotherapy for patients with
multifocal or multicentric disease, even if a complete
pathologic response was reached. We therefore analyzed
the survival of patients treated with neoadjuvant chemotherapy and breast conservation according to tumor focality
at diagnosis. Local relapse-free survival for multifocal and
multicentric disease did not differ from that for unifocal
1126
disease. However, among patients treated with mastectomy, those with multifocal but not multicentric disease
had a local relapse-free and disease-free survival advantage
over those with unifocal disease. This might be explained
by more frequent omission of postmastectomy radiotherapy
for patients with unifocal disease than for patients with
multifocal/multicentric disease. Unfortunately we lacked
information on the use of adjuvant radiotherapy in the
examined cohort, so we cannot support this hypothesis with
evidence. However, neither multifocality nor multicentricity were independent negative prognosticators for local
relapse-free survival when a pathologic complete response
was removed as a variable in Cox regression analysis.
In an earlier study by Oh et al. 706 patients receiving
anthracycline-based neoadjuvant chemotherapy, including
97 patients classified as clinically multifocal or multicentric, were examined.23 These authors found no statistical
difference in the locoregional relapse rate regardless of
locoregional treatment between unifocal and multifocal/
multicentric breast cancer patients. Likewise, no difference
between the two groups was found for 5-year disease-free
or overall survival. The authors concluded that clinically
detected multifocal or multicentric disease did not negatively influence the outcome for patients. Our results
support this finding only for patients treated with breast
conservation and those who achieve a pathologic complete
response. This might be explained by some important
differences between the Oh et al.23 study and ours. First,
our study analyzed a much larger cohort of patients within
each focality group, which provided more statistical power
to evaluate the impact of clinical focality after neoadjuvant
chemotherapy on survival. Second, in our study, 58 % of
the multifocal patients and 29 % of the multicentric
patients underwent breast conservation, whereas in the MD
Anderson Hospital cohort,28 breast conservation was performed only for patients with multifocal disease and not for
those with multicentric disease. Former retrospective
studies analyzing the outcome for patients with multifocal
or multicentric breast cancer in the adjuvant setting gave
controversial results. Weissenbacher et al.24 and Yerushalmi et al.25 reported a significantly better breast
cancer-specific survival for patients with unifocal cancer
than for those with multifocal or multicentric disease. In
contrast, in other studies,11,26,27 multifocal/multicentric
disease was not a predictor for a higher locoregional
relapse rate if adjustment was made for other risk factors.
A similar finding was reported by a recently published
adjuvant study from the MD Anderson Hospital,28 in which
locoregional recurrence-free survival of patients with
multifocal (n = 673) and multicentric (n = 233) disease
was reported. Breast conservation was performed for 62 %
of patients with unifocal tumors and 38 % of patients with
multifocal but not for patients with multicentric tumors. No
B. Ataseven et al.
patients needing mastectomy after neoadjuvant chemotherapy showed a higher risk for locoregional recurrence and
should therefore be monitored closely. Our findings should
encourage clinicians and patients to consider breast conservation after neoadjuvant chemotherapy if clear margins
and acceptable cosmetic results can be achieved even if the
tumor was initially diagnosed to be multifocal or
multicentric.
DISCLOSURE
None.
REFERENCES
1. Anastassiades O, Iakovou E, Stavridou N, Gogas J, Karameris A.
Multicentricity in breast cancer. A study of 366 cases. Am J Clin
Pathol. 1993;99:23843.
2. Egan RL. Multicentric breast carcinomas: clinical-radiographicpathologic whole-organ studies and 10-year survival. Cancer.
1982;49:112330.
3. Fisher ER, Gregorio R, Redmond C, Vellios F, Sommers SC,
Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4): I. Observations concerning
the multicentricity of mammary cancer. Cancer. 1975;35:24754.
4. McDivitt RW. Breast cancer multicentricity. Monogr Pathol.
1984(25):139148.
5. Sarnelli R, Squartini F. Multicentricity in breast cancer: a submacroscopic study. Pathol Ann. 1986;21(Pt 1):14358.
6. Spinelli C, Berti P, Ricci E, Miccoli P. Multicentric breast
tumour: an anatomical-clinical study of 100 cases. Eur J Surg
Oncol. 1992;18:236.
7. Vaidya JS, Vyas JJ, Chinoy RF, Merchant N, Sharma OP, Mittra
I. Multicentricity of breast cancer: whole-organ analysis and
clinical implications. Br J Cancer. 1996;74:8204.
8. Wilson LD, Beinfield M, McKhann CF, Haffty BG. Conservative
surgery and radiation in the treatment of synchronous ipsilateral
breast cancers. Cancer. 1993;72:13742.
9. Leopold KA, Recht A, Schnitt SJ, et al. Results of conservative
surgery and radiation therapy for multiple synchronous cancers of
one breast. Int J Radiat Oncol Biol Phys. 1989;16:116.
10. Kurtz JM, Jacquemier J, Amalric R, et al. Breast-conserving
therapy for macroscopically multiple cancers. Ann Surg.
1990;212:3844.
11. Gentilini O, Botteri E, Rotmensz N, et al. Conservative surgery in
patients with multifocal/multicentric breast cancer. Breast Cancer Res Treat. 2009;113:57783.
12. Yerushalmi R, Tyldesley S, Woods R, Kennecke HF, Speers C,
Gelmon KA. Is breast-conserving therapy a safe option for
patients with tumor multicentricity and multifocality? Ann Oncol.
2012;23:87681.
13. Gianni L, Baselga J, Eiermann W, et al. Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by
cyclophosphamide, methotrexate, and fluorouracil and its effects
on tumor response as preoperative therapy. Clin Cancer Res.
2005;11(24 Pt 1):871521.
1127
14. Kaufmann M, von Minckwitz G, Mamounas EP, et al. Recommendations from an international consensus conference on the
current status and future of neoadjuvant systemic therapy in
primary breast cancer. Ann Surg Oncol. 2012;19:150816.
15. Huober J, Fasching PA, Hanusch C, et al. Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients
with nonresponsive tumours to epirubicin/cyclophosphamide
(EC) bevacizumab results of the randomised GeparQuinto
study (GBG 44). Eur J Cancer. 2013;49:228493.
16. Untch M, Loibl S, Bischoff J, et al. Lapatinib versus trastuzumab
in combination with neoadjuvant anthracycline-taxane-based
chemotherapy (GeparQuinto, GBG 44): a randomised phase 3
trial. Lancet Oncol. 2012;13:13544.
17. Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with
trastuzumab in HER2-positive breast cancer: results from the
GeparQuattro study. J Clin Oncol. 2010;28:202431.
18. von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant
chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299309.
19. von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in
addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III
GeparQuattro study. J Clin Oncol. 2010;28:201523.
20. von Minckwitz G, Blohmer JU, Costa SD, et al. Response-guided
neoadjuvant chemotherapy for breast cancer. J Clin Oncol.
2013;31:362330.
21. von Minckwitz G, Kummel S, Vogel P, et al. Neoadjuvant
vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III
randomized GeparTrio trial. J Nat Cancer Inst. 2008;100:54251.
22. von Minckwitz G, Kummel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III
randomized GeparTrio study. J Nat Cancer Inst. 2008;100:552
62.
23. Oh JL, Dryden MJ, Woodward WA, et al. Locoregional control
of clinically diagnosed multifocal or multicentric breast cancer
after neoadjuvant chemotherapy and locoregional therapy. J Clin
Oncol. 2006;24:49715.
24. Weissenbacher T, Zschage M, Janni W, et al. Multicentric and
multifocal versus unifocal breast cancer: is the tumor-nodemetastasis classification justified? Breast Cancer Res Treat.
2010;122:2734.
25. Yerushalmi R, Kennecke H, Woods R, Olivotto I, Speers C,
Gelmon K. Does multicentric/multifocal breast cancer differ from
unifocal breast cancer? An analysis of survival and contralateral
breast cancer incidence. Breast Cancer Res Treat. 2009;117:365
70.
26. Kadioglu H, Yucel S, Yildiz S, et al. Feasibility of breast conserving surgery in multifocal breast cancers. Am J Surg.
2014;208:45764.
27. Lynch SP, Lei X, Chavez-MacGregor M, et al. Multifocality and
multicentricity in breast cancer and survival outcomes. Annl
Oncol. 2012;23:30639.
28. Lynch SP, Lei X, Hsu L, et al. Breast cancer multifocality and
multicentricity and locoregional recurrence. Oncologist. 2013;
18:116773.
29. Moon HG, Han W, Kim JY, et al. Effect of multiple invasive foci
on breast cancer outcomes according to the molecular subtypes: a
report from the Korean Breast Cancer Society. Ann of Oncol.
2013;24:2298304.