Risk factors for breast cancer development by tumor characteristics among women with benign breast disease

Figueroa, Jonine D.; Gierach, Gretchen L.; Duggan, Máire A.; Fan, Shaoqi; Pfeiffer, Ruth M.; Wang, Yihong; Falk, Roni T.; Loudig, Olivier; Abubakar, Mustapha; Ginsberg, Mindy; Kimes, Teresa M.; Richert-Boe, Kathryn; Glass, Andrew G.; Rohan, Thomas E.

doi:10.1186/s13058-021-01410-1

Breast Cancer Research

Table 1 Characteristics of BBD histology among breast cancer cases, overall and by age and ER status at breast cancer diagnosis (N = 514)

From: Risk factors for breast cancer development by tumor characteristics among women with benign breast disease

			Age at breast cancer diagnosis					ER status
	Cases		≤ 50 years (N = 69)		> 50 years (N = 445)		P^a	ER+ (N = 391)		ER− (N = 64)		P^a
	N	%	N	%	N	%	P^a	N	%	N	%	P^a
Age at BBD, years
< 40	90	17.5	41	59.4	49	11.0	< 0.0001	61	15.6	13	20.3	0.83
40–49	141	27.4	28	40.6	113	25.4		113	28.9	17	26.6
50–59	145	28.2	0	0	145	32.6		111	28.4	19	29.7
60–69	86	16.7	0	0	86	9.3		65	16.6	8	12.5
≥ 70	52	10.1	0	0	52	11.7		41	10.5	7	10.9
Mean (SD)	52.2 (12.5)		37.5 (6.9)		54.4 (11.6)			52.4 (12.5)		51.7 (12.9)
Median (IQR)	51.5 (42.6, 60.8)		39.0 (34.9, 42.9)		53.6 (46.1, 62.1)			51.7 (42.8, 61.0)		50.6 (42.8, 59.8)
Year of BBD diagnosis							0.062					0.92
1971–1979	95	18.5	19	27.5	76	17.1		50	12.8	10	15.6
1980–1989	173	33.7	16	23.2	157	35.3		134	34.3	20	31.3
1990–1999	161	31.3	25	36.2	136	30.6		134	34.3	22	34.4
2000–2006^#	85	16.5	9	13.0	76	17.1		73	18.7	12	18.8
BBD histology							0.22					0.39
Normal/non-proliferative	324	63.0	50	72.5	274	61.6		243	62.2	43	67.2
Proliferative without atypia	163	31.7	16	23.2	147	33.3		127	32.5	20	31.3
Proliferative with atypia	27	5.3	3	4.4	24	5.4		21	5.4	1	1.6
Year of breast cancer diagnosis							< 0.0001					0.53
1973–1990	72	14.1	22	31.9	51	11.4		21	5.4	3	4.7
1991–1995	68	13.2	10	14.5	58	13.0		49	12.5	12	18.8
1996–2000	101	19.7	17	24.6	84	18.8		81	20.7	17	26.6
2001–2005	116	22.6	11	15.9	106	23.7		104	26.6	12	18.8
2006–2010	106	20.6	5	7.3	101	22.6		91	23.3	14	21.9
2011–2013	51	9.9	4	5.8	47	10.6		45	11.5	6	9.4
Years from BBD to breast cancer diagnosis							< 0.0001					0.55
≤ 10	284	55.3	54	78.3	230	51.7		198	50.6	35	54.7
> 10	230	44.8	15	21.7	215	48.3		193	49.4	29	45.3
Mean (SD)	10.8 (7.9)		7.3 (6)		11.4 (8)			11.6 (8)		10.5 (8.3)
Median (IQR)	9.0 (4.4, 15.8)		5.6 (2.9, 9.4)		9.8 (4.7, 16.3)			10.0 (5.3, 16.4)		8.7 (3.3, 15.7)
Tumor size/mm							0.13					0.63
< 10	143	28.9	26	37.7	117	27.5		90	23.9	16	26.2
10–20	211	42.6	29	42.0	182	42.7		173	45.9	24	39.3
> 20	141	28.5	14	20.3	127	29.8		114	30.2	21	34.4
Missing	19		0		19			14		3
Tumor grade^c							0.14					< 0.0001
Well differentiated	141	34.7	14	31.8	127	34.9		134	39.3	5	8.6
Moderately differentiated	159	38.9	13	29.6	146	40.1		149	43.7	6	10.3
Poorly differentiated	108	26.4	17	38.6	91	25.0		58	17.0	47	81.0
Not determined	106		25		81			50		6
ER							0.026					–
Negative	64	14.1	12	24.5	52	12.8		–	–	–	–
Positive	391	85.9	37	75.5	354	87.2		–	–	–	–
Missing/unknown	59		20		39			–	–	–	–
PR							0.53					< 0.0001
Negative	131	28.9	16	32.7	115	28.4		73	18.7	58	90.6
Positive	323	71.2	33	67.4	290	71.6		317	81.3	6	9.4
Missing/unknown	60		20		40			1		0
HER2^d							0.99^b					0.0028
Negative	224	79.4	17	73.9	207	79.9		203	81.5	20	62.5
Positive	50	17.7	4	17.4	46	17.8		38	15.3	12	37.5
Equivocal	8	2.8	2	8.7	6	2.3		8	3.2	0	0.0
Missing/unknown	232		46		186			142		32
Regional lymph nodes							0.98					0.11
Negative	337	73.6	47	73.4	230	73.6		264	74.6	36	64.3
Positive	121	26.4	17	26.6	104	26.4		90	25.4	20	35.7
Missing	56		5		51			37		8
Tumor histology							0.54^b					0.14^b
Ductal	439	83.5	59	85.5	370	83.2		322	82.4	54	84.4
Lobular	48	9.3	8	11.6	40	9.0		39	10.0	4	6.3
Mixed ductal/lobular	26	5.1	2	2.9	24	5.4		23	5.9	2	3.1
Others	11	2.1	0	0.0	11	2.5		7	1.8	4	6.3
Tumor stage							0.46^b					0.30^b
I	262	58.0	32	62.8	230	57.4		223	59.3	29	47.5
II	150	33.2	13	25.5	137	34.2		120	31.9	25	41.0
III	29	6.4	4	7.8	25	6.2		24	6.4	5	8.2
IV	11	2.4	2	3.9	9	2.2		9	2.4	2	3.3
Missing	62		18		44			15		3

Among all cases, 13.4% were diagnosed with breast cancer by 50 years old versus 86.6% were diagnosed after age at 50 years. Fifty-nine cases who had missing ER status were excluded from analyses with ER status. BBD benign breast disease, ER estrogen receptor status, HER2 human epidermal growth factor, IQR inter-quartile range, PR progesterone receptor status, SD standard deviation. ^aP-values from the chi-square test except where noted; cases with missing tumor characteristics were excluded from reported percentage and tests; P-values less than 0.05 are in bold font. ^bP-values from the Fisher exact test. ^cPatients with tumor grade as “not determined” were excluded from analysis. ^dPatients with equivocal HER2 were excluded from the analysis. Involution and columnar cell lesion associations were adjusted for all factors above the line indicated in OR*. ^#One control had a BBD diagnosis in 2012

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