Pilot study investigating the prognostic significance of thymidine phosphorylase expression in patients with metastatic breast cancer: a single institution retrospective analysis

Figures & data

Figure 1 Metabolic conversion of the prodrug capecitabine to the active antimetabolite moiety, 5-fluorouracil.

Figure 2 Immunohistochemistry showing TP expression in carcinoma of the breast (magnification, 400×). Representative images of immunohistochemistry staining patterns for mixed nuclear/cytoplasmic TP protein in normal epithelium and in primary or metastatic lesions.

Notes: (A) Normal mammary ductal epithelium showing moderate staining (+2) of TP, (B) DCIS showing moderate staining (+2) of TP, (C) invasive carcinoma showing moderate staining (+2) of TP, (D) DCIS showing weak staining (+1) of TP, (E) invasive carcinoma showing weak staining (+1) of TP, (F) DCIS showing no staining (0) of TP, (G) invasive carcinoma showing no staining (0) of TP, and (H) nuclear staining of Ki67.
Abbreviations: DCIS, ductal carcinoma in situ; TP, thymidine phosphorylase.

Table 1 Patient tumor characteristics

ID	Age at diagnosis, years	Type of biopsy	Type of BC	Stage	TP expression in DCIS and ILC/IDC		Ki67	Receptor status
					DCIS	ILC/IDC		ER	PR	HER2
1	70	Surgical	IDC	IV	+2	+2	13%	−	−	−
2	55	Surgical	IDC	IV	Not present	+1	59%	−	−	−
3	51	Surgical	IDC	IV	Not present	+1	26%	−	−	−
4	51	Surgical	IDC	IV	0	0	60%	−	−	−
5	56	Surgical	IDC	IV	Not present	0	24%	−	−	+
6	45	Surgical	IDC	IV	+2	+2	26.5%	−	−	+
7	49	Surgical	IDC	IV	+2	+1	25%	+	+	N/A
8	72	Surgical	IDC	IV	Not present	0	22.5%	+	−	−
9	65	Surgical	IDC	IV	Not present	0	50%	+	+	+
10	48	Metastatic lesion	ILC	IV	Not present	0	26%	+	+	−
11	62	Metastatic lesion	IDC	IV	Not present	0	15%	+	+	+
12	54	Surgical	IDC	IV	+2	0	33.5%	+	+	−
13	43	Metastatic lesion	ILC	IV	Not present	0	20%	+	+	−
14	59	Surgical	ILC	IV	Not present	0	1%	+	+	−
15	56	Surgical	IDC	IV	+1	0	14%	+	+	−
16	83	Surgical	IDC	IV	Not present	+1	30.5%	+	−	−
17	65	Surgical	IDC	IV	+2	+1	37.5%	+	−	+
18	41	Needle	IDC	III	Not present	0	37.5%	+	+	+

Abbreviations: BC, breast cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; PR, progesterone receptor; ILC, invasive lobular carcinoma; IDC, invasive ductal carcinoma; TP, thymidine phosphorylase; N/A, not available.

Table 2 Relationship between patient ER-positive/negative receptor status and tumoral TP expression, and the clinical benefit to a capecitabine-based chemotherapeutic regimen measured as TTP

ID	Stage and type of BC	TP expression in DCIS and ILC/IDC		Ki67	Receptor status			TTP on capecitabine-based therapy
		DCIS1	ILC/IDC2		ER	PR	HER2
ER-negative group
1	Stage IV; IDC	+2	+2	13%	−	−	−	9 months
2	Stage IV; IDC	Not present	+1	59%	−	−	−	15 months
3	Stage IV; IDC	Not present	+1	26%	−	−	−	5 months
4	Stage IV; IDC	0	0	60%	−	−	−	2 months
5	Stage IV; IDC	Not present	0	24%	−	−	+	6 months
6	Stage IV; IDC	+2	+2	26.5%	−	−	+	9 months
ER-positive group
7	Stage IV; IDC	+2	+1	25%	+	+	N/A	19 months
8	Stage IV; IDC	Not present	0	22.5%	+	−	−	2 months
9	Stage IV; IDC	Not present	0	50%	+	+	+	4 months
10	Stage IV; ILC	Not present	0	26%	+	+	−	33 months
11	Stage IV; IDC	Not present	0	15%	+	+	+	30 months
12	Stage IV; IDC	+2	0	33.5%	+	+	−	7 months
13	Stage IV; ILC	Not present	0	20%	+	+	−	6 months
14	Stage IV; ILC	Not present	0	1%	+	+	−	36 months and still on it
Patients who discontinued due to adverse events
15	Stage IV; IDC	+1	0	14%	+	+	−	Dizzy; ~12 days
16	Stage IV; IDC	Not present	+1	30.5%	+	−	−	Developed colitis secondary to capecitabine, hand/foot syndrome, bloody diarrhea; ~2 months
17	Stage IV; IDC	+2	+1	37.5%	+	−	+	Recurrent diarrhea; ~3 months
18	Locally advanced stage III; IDC	Not present	0	37.5%	+	+	+	Poor tolerance to capecitabine, flare-up of Crohn’s disease and blurred vision; ~1 month

Notes:

1,2 TP intensity of cytoplasmic and nuclear staining was categorized into 0, 1, 2, or 3, denoting 0 (no), 1 (weak), 2 (moderate), and 3 (strong) staining, respectively. The LCIS component was not present in any of the specimens.

Abbreviations: BC, breast cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; PR, progesterone receptor; ILC, invasive lobular carcinoma; IDC, invasive ductal carcinoma; TTP, time to progression; TP, thymidine phosphorylase; N/A, not available.