Primary neuroendocrine breast carcinomas: a retrospective analysis and review of literature

Figures & data

Table 1 The clinical information of primary NEBC patients at diagnosis

Number	Gender	Age (years)	Location	Diagnosis date, month/year	Single/multiple lesions	Tumor size (mm)	Surgical treatment	Lymph node (LN)	Stage
1	Female	61	Left	01/2015	Single	14	MRA + SLNB + ALND	2/15	II
2	Female	77	Left	08/2015	Single	15	MRA + ALND	0/11	I
3	Female	17	Left	06/2014	Multiple (2)	33 and 18	No	Bilateral neck, left supraclavicular and mediastinum LN, pleura	IV
4	Female	57	Left	03/2014	Single	35	Mastectomy + SLNB	0/1	II
5	Female	64	Left	03/2012	Single	16	MRA + ALND	0/13	I
6	Female	65	Left	11/2011	Single	24	MRA + ALND	0/18	II
7	Female	45	Left	11/2011	Single	8	MRA + ALND	0/14	I
8	Female	46	Right	05/2011	Single	31	MRA + ALND	2/16	II
9	Female	43	Right	10/2006	Single	30	MRA + ALND	0/8	II
10	Female	58	Right	04/2009	Single	24	MRA + ALND subcutaneous	11/12	III
11	Female	41	Right	03/2010	Multiple (3)	Max: 10	Mastectomy + ALND + breast reconstruction	4/13	II
12	Female	79	Left	12/2009	Single	20	MRA + ALND	0/11	I
13	Female	82	Right	07/2008	Single	130 (with ulceration)	Mastectomy	0/2	III
14	Female	53	Left	11/2007	Single	75	MRA + ALND	0/17	II
15	Female	69	Right	05/2007	Single	15	MRA + ALND	0/30	I
16	Female	77	Left	03/2008	Single	45	MRA + ALND	0/17	II
17	Female	50	Right	06/2005	Single	15	MRA + ALND	0/13	I
18	Female	65	Right	07/2005	Single	Unknown	MRA + ALND	0/17	Unknown
19	Female	76	Left	12/2005	Single	50	MRA + ALND	0/13	II

Abbreviations: NEBC, neuroendocrine breast carcinoma; MRA, modified radical mastectomy; SLNB, sentinel lymph node biopsy; ALND, axillary lymph node dissection.

Table 2 The immunohistochemistry of primary NEBC patients

Number	ER	PR	HER-2/FISH	CgA	Syn	NSE	CD56	Ki67 (%)	P53 (%)
1	P	N	(2+)/N	N	P	P	N	20	<5
2	P	P	N	P	P	N	N	5	N
3	N	N	None	N	P	None	P	80	P
4	P	P	N	P	P	None	N	3	N
5	P	P	N	N	N	P	None	<5	P
6	P	P	(2+)/N	N	P	P	None	80	50
7	P	P	(2+)/N	N	N	P	None	<3	P
8	P	P	N	N	P	P	None	50	5
9	P	P	N	P	P	None	None	None	N
10	P	N	N	P	P	None	N	None	N
11	P	P	N	P	N	P	None	10	5
12	P	P	N	N	P	P	None	5	N
13	None	None	None	P	P	N	None	None	None
14	P	P	(2+)/none	N	P	P	None	None	N
15	P	P	N	P	P	P	P	None	N
16	None	None	None	P	P	None	None	None	None
17	None	None	None	N	None	P	None	None	None
18	P	N	N	N	N	P	None	None	N
19	None	None	None	N	P	P	None	None	None

Abbreviations: NEBC, neuroendocrine breast carcinoma; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2; FISH, fluorescent in situ hybridization; CgA, chromogranin A; Syn, synaptophysin; NSE, neuron-specific enolase; P, positive; N, negative.

Table 3 The adjuvant therapy and clinical follow-up of primary NEBC patients

Number	Neochemotherapy	Chemotherapy	Radiotherapy	Endocrine therapy	Follow-up (months)	Recurrence and metastasis	Survival
1	No	Yes, EC-T	Not required	No	15.5	No	Yes
2	No	No	Not required	Yes, exemestane	16.4	No	Yes
3	Yes, EP	No	Yes	Not required	22.9	Yes, bilateral neck, left supraclavicular and mediastinum LN, pleura	Yes
4	No	Yes, TEC*	Not required	Yes, letrozole	25.3	No	Yes
5	No	Yes, TC	Not required	Yes, anastrozole	49.5	No	Yes
6	No	Yes, TEC*	Not required	Yes, anastrozole	53.6	No	Yes
7	No	Yes, TEC	Not required	Yes, tamoxifen	53.9	No	Yes
8	No	Yes, TT#C	Not required	Yes, exemestane	59.4	No	Yes
9	No	Yes, TP	Not required	Yes, tamoxifen	114	Yes, brain	Yes
10	Yes, TAC	Yes, TAC	Yes	Yes, anastrozole	85	Yes, bone and liver	Yes
11	No	Yes, TEC	Unknown	Unknown	73.4	Unknown	Unknown
12	No	No	Not required	No	57.7	No	Death
13	No	No	Not required	Unknown	52.4	No	Death
14	No	Yes, CEF	Not required	Unknown	101.5	Unknown	Unknown
15	No	Yes, CT#F	Not required	Unknown	107.3	Unknown	Unknown
16	No	No	Not required	Unknown	Unknown	Unknown	Unknown
17	No	Unknown	Not required	Unknown	Unknown	Unknown	Unknown
18	No	Unknown	Not required	Unknown	Unknown	Unknown	Unknown
19	No	No	Not required	Unknown	Unknown	Unknown	Unknown

Notes:

# T: pirarubicin (THP).

* Not finished entire planned chemotherapy.

Abbreviations: NEBC, neuroendocrine breast carcinoma; E, epirubicin; C, cyclophosphamide; T, docetaxel; F, fluorouracil (5-Fu); P, cis-platinum; LN, lymph node.

Figure 1 CT image of the patient with hepatic metastasis in September 2012, 70 months after the initial surgical treatment.

Notes: (A and B) The image of plain scan showed that the density of liver parenchyma was diffusely reduced, and extensive round-like higher density lesions in the liver. (C and D) Enhanced CT revealed multiple nodular enhancement in liver.
Abbreviation: CT, computed tomography.

Figure 2 Post-therapy abdominal CT of the patient with hepatic metastasis in April 2013.

Note: Over a period of 7 months of treatment, both (A and B) plain scan and (C and D) enhanced CT showed that the hepatic lesions were gradually decreased.
Abbreviation: CT, computed tomography.

Figure 3 Post-therapy abdominal CT of the patient with hepatic metastasis in May 2014.

Note: With 20 months of treatment, the hepatic lesions were further reduced in both (A and B) plain scan and (C and D) enhanced CT.
Abbreviation: CT, computed tomography.

Figure 4 Surveillant CT.

Notes: (A and B) The CT of the abdomen showed that the hepatic metastasis lesions of this patient progressed again in October 2014. (C and D) After a modified therapy, the reduction of hepatic lesions was obviously found by CT of the abdomen in February 2015.
Abbreviation: CT, computed tomography.

Table S1 Mammography features of NEBC

Number	Presentation	Location	Shape	Margins	Density	Calcification	BI-RADS
1	Mass	LUOQ	Round	Indistinct	High	Clustered	4C
2	Mass	LUOQ	Round	Indistinct	High	None	4B
3	Mass	LLOQ	Oval	Well defined	High	None	0
4	Mass	LUIQ	Oval	Well defined	High	None	4B
5	Nondetectable						0
6	Mass	LLOQ	Irregular	Circumscribed	High	Micro	4A
7	Mass	LU	Irregular	Indistinct	High	Micro	4C
8	Nondetectable
9	Unknown
10	Distortion	RUOQ	Not obvious	Indistinct	Isodensity	Needle like	5
11	Calcification	RUOQ	Not obvious	Not obvious	High	Sand like	6
12	Mass	LUOQ	Irregular	Spiculate	High	None	5
13	Not done
14	Mass	LUOQ	Irregular	Indistinct	High	Sand like	Unknown
15	Mass	RUOQ	Lobulated	Spiculate	High	None	6

Abbreviations: NEBC, neuroendocrine breast carcinoma; BI-RADS, Breast Imaging-Reporting and Data System; LUOQ, left upper outer quadrant; LLOQ, left lower outer quadrant; LUIQ, left upper inner quadrant; LU, left upper; RUOQ, right upper outer quadrant.

Table S2 Ultrasonography features of NEBC

Number	Shape	Margins	Echogenicity	Calcification	Color Doppler	Lymph node enlargement
1	Round	Indistinct	Hypoechoic	Punctiform	Increased blood supply	Yes
2	Round	Indistinct	Hypoechoic	None	None	No
3	Oval	Well defined	Hypoechoic	None	High-velocity blood flow	Yes
4	Oval	Well defined	Hypoechoic	None	High-velocity blood flow	Yes
5	Irregular	Indistinct	Hypoechoic	None	None	No
6	Irregular	Indistinct	Heterogeneous	None	Increased blood supply	Yes
7	Irregular	Spiculate	Heterogeneous	None	None	No
8	Irregular	Crab like	Heterogeneous	None	Increased blood supply	No
9	Unknown
10	Lobulated	Indistinct	Heterogeneous	Clustered	Increased blood supply	Yes
11	Oval	Indistinct	Heterogeneous	None	None	Yes
12	Irregular	Indistinct	Heterogeneous	Punctiform	Increased blood supply	Yes
13	Not done
14	Irregular	Crab like	Heterogeneous	None	Increased blood supply	No
15	Irregular	Crab like	Heterogeneous	Punctiform	Increased blood supply	No

Abbreviation: NEBC, neuroendocrine breast carcinoma.