Contralateral breast cancer can represent a metastatic spread of the first primary tumor: determination of clonal relationship between contralateral breast cancers using next-generation whole genome sequencing

Table 1 Clinical characteristics

Patient	Tumor	Laterality	Age at BC1	Histology	Multicentric	Size (mm)	Lymph node metastasis^a	ER	PR	HER2^b	Ki67	NHG	Treatment	Time interval BC1 – BC2 (months)	Metastasis after BC2^c (months, location)
1	BC1	Left	61	Lobular	No	32	No (0/4)	Pos	Pos	UK	UK	2	Tam	61	Yes (15, lung, liver, skeleton)
	BC2	Right		DCIS	Yes	14	No (0/3)	NA	NA	NA	NA	3	None
2	BC1	Left	41	Ductal	No	15	No (0/10)	Pos	Pos	UK	UK	2	None	5	No (249)
	BC2	Right		Ductal	No	14	No (0/5)	Pos	Pos	2+	9 %	3	None
3	BC1	Left	83	Ductal	No	17	No (0/11)	Neg	Neg	Neg	30 %	3	None	23	No (8)
	BC2	Right		Ductal	No	25	No (0/12)	Neg	Neg	Neg	75 %	3	None
4	BC1	Left	51	Ductal	No	25	Yes (9/21, PG)	Neg	Pos	3+	14 %	3	RT, CT (7 CMF)	24	No (61)
	BC2	Right		Ductal	No	25	Yes (7/28, PG)	Pos	Pos	Neg	16 %	3	RT, Tam
5	BC1	Left	43	Ductal	No	10	No (0/23)	Neg	Neg	Neg	80 %	3	RT, CT (9 CMF)	22	Yes (13, liver)
	BC2	Right		Ductal	No	20	No (0/20)	Neg	Neg	Neg	27 %	3	RT
6	BC1	Right	51	Lobular	Yes	70	Yes (3/8, PG)	Pos	Pos	Neg	28 %	2	RT, CT (9 CMF)	17	Yes (5, brain)
	BC2	Left		Lobular	Yes	12	Yes (23/26, PG)	Pos	Neg	Neg	22 %	2	CT (3 Doxo–2 T)
7	BC1	Right	52	Ductal	No	16	No (0/11)	Pos	Pos	Neg	21 %	3	RT, Tam	30	No (66)
	BC2	Left		Ductal	No	16	No (0/1)	Neg	Neg	Neg	40 %	3	CT (6 FEC)
8	BC1	Left	46	Lobular	No	80	Yes (33/34, PG)	Pos	Pos	Neg	4 %	3	RT, CT (9 FEC)	11	Yes (16, lung)
	BC2	Right		Lobular	Yes	55	Yes (11/25, PG)	Pos	Pos	Neg	5 %	2	RT, Tam + oophorectomy
9^d	BC1	Right	63	Ductal	No	28	Yes (2/13)	Pos	Pos	Neg	UK	2	Tam–AI	0	Yes (62, skeleton)
	BC2	Left		Ductal	No	55	Yes (1/12)	Pos	Pos	Neg	UK	3	RT, Tam–AI
10	BC1	Right	32	Ductal	No	23	No (0/1)	Neg	Neg	UK	UK	3	RT, CT (6 FEC)	35	Yes (13, skin)
	BC2	Left		Ductal	No	45	Yes (12/12)	Neg	Neg	Neg	UK	2	RT

AI aromatase inhibitor, BC1 first breast cancer, BC2 second breast cancer, CMF cyclophosphamide, methotrexate and fluorouracil, CT chemotherapy (cycles and regime used in parentheses), DCIS ductal carcinoma in situ, Doxo doxorubicin, ER estrogen receptor, FEC fluorouracil, epirubicin, and cyclophosphamide, HER2 human epidermal growth factor receptor 2, NA not applicable, Neg negative, NHG Nottingham histological grade, PG periglandular growth, Pos positive, PR progesterone receptor, RT radiotherapy, T docetaxel, Tam tamoxifen, UK unknown
^aNumber of positive lymph nodes/number of investigated nodes in parentheses
^bHER2 determined with immunohistochemistry (Herceptest) where score 0–1 has been classified as negative. For score 2+ and 3+ the individual score is given in the table
^cIf the patient developed metastases, the time interval between BC2 and diagnosis of metastasis (months) and the site of the first metastasis is given within parentheses. In patients who do not develop metastases, the follow-up period (months) is given within parentheses
^dPatient 9 was diagnosed with her left and right breast cancer simultaneously (synchronous contralateral breast cancer), hence it cannot be said which tumor was first

ISSN: 1465-542X