Prognostic comparison between breast-conserving surgery combined with radiotherapy and total mastectomy in patients with triple-negative invasive lobular carcinoma: a SEER database-based study

doi:10.16139/j.1007-9610.2025.03.12

Abstract

Abstract:

Objective To investigate the prognosis of patients with triple-negative invasive lobular carcinoma (TN-ILC) undergoing breast-conserving surgery combined with radiotherapy (BCS+RT) versus total mastectomy. Methods A retrospective analysis was performed for 2 386 female patients with TN-ILC who underwent surgery in the SEER database from 2006 to 2018, and the baseline characteristics (age, histological grade, AJCC stage, etc.) were balanced by propensity score matching (PSM, 1∶1, caliper value 0.02), and breast cancer-specific survival (BCSS) and overall survival (OS) were compared by Kaplan-Meier method and COX regression analysis. Results A total of 1 056 pairs of patients were obtained after PSM, and the BCS+RT group had significantly better BCSS and OS than the total mastectomy group (both P<0.001). Stratified analyses showed that BCS+RT had a survival advantage in all subgroups except histologic grade Ⅰ and tumor stage Ⅰ. Multivariate analysis confirmed that BCS+RT was an independent protective factor (BCSS: HR=0.682, OS: HR=0.607, both P<0.001). Conclusions BCS+RT significantly improves survival compared with total mastectomy in patients with TN-ILC, supporting BCS+RT as the preferred treatment strategy for eligible patients.

Key words: Triple-negative invasive lobular carcinoma(TN-ILC), Breast-conserving surgery(BCS), Total mastectomy, Overall survival(OS), Breast cancer-specific survival(BCSS)

CLC Number:

R737.9

WANG Xinping, YU Zhun, YUAN Shuai, TANG Yongzhe. Prognostic comparison between breast-conserving surgery combined with radiotherapy and total mastectomy in patients with triple-negative invasive lobular carcinoma: a SEER database-based study[J]. Journal of Surgery Concepts & Practice, 2025, 30(03): 256-263.

Figures/Tables 6

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References 28

[1]	AUTIER P, BONIOL M, LA VECCHIA C, et al. Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database[J]. BMJ, 2010,341:c3620.
[2]	HOWLADER N, ALTEKRUSE S F, LI C I, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status[J]. J Natl Cancer Inst, 2014, 106(5):dju055.
[3]	DESANTIS C E, MA J, GAUDET M M, et al. Breast cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(6):438-451.
[4]	DENT R, TRUDEAU M, PRITCHARD K I, et al. Triple-negative breast cancer: clinical features and patterns of recurrence[J]. Clin Cancer Res, 2007, 13(15 Pt 1):4429-4434.
[5]	National Cancer Institute. Cancer stat facts: female breast cancer subtypes[EB/OL]. [2025-04-09]. https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
[6]	MONTAGNA E, MAISONNEUVE P, ROTMENSZ N, et al. Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome[J]. Clin Breast Cancer, 2013, 13(1):31-39. doi: 10.1016/j.clbc.2012.09.002 pmid: 23098574
[7]	BERGERON A, MACGROGAN G, BERTAUT A, et al. Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations[J]. Mod Pathol, 2021, 34(7):1282-1296.
[8]	ABDULKARIM B S, CUARTERO J, HANSON J, et al. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy[J]. J Clin Oncol, 2011, 29(21):2852-2858. doi: 10.1200/JCO.2010.33.4714 pmid: 21670451
[9]	FISHER B, BAUER M, MARGOLESE R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer[J]. N Engl J Med, 1985, 312(11):665-673.
[10]	FISHER B, ANDERSON S, BRYANT J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer[J]. N Engl J Med, 2002, 347(16):1233-1241.
[11]	BLICHERT-TOFT M, NIELSEN M, DÜRING M, et al. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol[J]. Acta Oncol, 2008, 47(4):672-681.
[12]	VERONESI U, CASCINELLI N, MARIANI L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer[J]. N Engl J Med, 2002, 347(16):1227-1232.
[13]	VAN MAAREN M C, DE MUNCK L, DE BOCK G H, et al. 10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study[J]. Lancet Oncol, 2016, 17(8):1158-1170. doi: S1470-2045(16)30067-5 pmid: 27344114
[14]	ADKINS F C, GONZALEZ-ANGULO A M, LEI X, et al. Triple-negative breast cancer is not a contraindication for breast conservation[J]. Ann Surg Oncol, 2011, 18(11):3164-3173. doi: 10.1245/s10434-011-1920-z pmid: 21947595
[15]	DANISH H H, GOYAL S, TAUNK N K, et al. Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) as a prognostic marker for local control in T1-2 N0 breast cancer treated with breast-conserving surgery and radiation therapy (BCS + RT)[J]. Breast J, 2013, 19(3):231-239.
[16]	CONFORTI F, PALA L, PAGAN E, et al. Biological and clinical features of triple negative invasive lobular carcinomas of the breast. Clinical outcome and actionable molecular alterations[J]. Breast, 2021,59:94-101.
[17]	AMIN M B, EDGE S B, GREENE F L, et al. AJCC Cancer Staging Manual[M]. 8th ed. New York: Springer,2016:621-624.
[18]	SIMONE N L, DAN T, SHIH J, et al. Twenty-five year results of the national cancer institute randomized breast conservation trial[J]. Breast Cancer Res Treat, 2012, 132(1):197-203.
[19]	LITIÈRE S, WERUTSKY G, FENTIMAN I S, et al. Breast conserving therapy versus mastectomy for stage Ⅰ-Ⅱ breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial[J]. Lancet Oncol, 2012, 13(4):412-419.
[20]	BHOO-PATHY N, VERKOOIJEN H M, WONG F Y, et al. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer: a historical cohort study[J]. Int J Cancer, 2015, 137(10):2504-2512.
[21]	GOLDEN E B, FRANCES D, PELLICCIOTTA I, et al. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death[J]. Oncoimmunology, 2014,3:e28518.
[22]	VANPOUILLE-BOX C, DIAMOND J M, PILONES K A, et al. TGFβ is a master regulator of radiation therapy-induced antitumor immunity[J]. Cancer Res, 2015, 75(11):2232-2242.
[23]	MOZDARANI H. Biological complexities in radiation carcinogenesis and cancer radiotherapy: impact of new biological paradigms[J]. Genes(Basel), 2012, 3(1):90-114.
[24]	POGODA K, NIWIŃSKA A, SARNOWSKA E, et al. Effects of BRCA germline mutations on triple-negative breast cancer prognosis[J]. J Oncol, 2020,2020:8545643.
[25]	WAN A, ZHANG G, MA D, et al. An overview of the research progress of BRCA gene mutations in breast cancer[J]. Biochim Biophys Acta Rev Cancer, 2023, 1878(4):188907.
[26]	LIN A, SHARIEFF W, JUHASZ J, et al. The benefit of deep inspiration breath hold: evaluating cardiac radiation exposure in patients after mastectomy and after breast-conserving surgery[J]. Breast Cancer, 2017, 24(1):86-91. doi: 10.1007/s12282-016-0676-5 pmid: 26886584
[27]	秦春新. 乳腺浸润性小叶癌临床病理特征及保乳切缘阳性的危险因素[D]. 辽宁: 大连医科大学, 2014.
	QIN C X. Clinical and pathological characteristics of invasive lobular carcinoma of the breast and risk factors for positive breast conserving margins[D]. Liaoning: Dalian Medical University, 2014.
[28]	颜敏, 顾瑞香, 王海强, 等. 新辅助化疗在乳腺浸润性小叶癌与浸润性导管癌患者的应用[J]. 江苏医药, 2020, 46(8):840-842.
	YAN M, GU R X, WANG H Q, et al. Application of neoadjuvant chemotherapy in patients with invasive lobular carcinoma and invasive ductal carcinoma[J]. Jiangsu Med J, 2020, 46(8):840-842.

Characteristics		BCS+RT(n=1 124)	Mastectomy（n=1 262）	Total(n=2 386)	χ² value	P value
Median follow-up (months)		27（10-48）	29(11-49)	28(10-48)
Median age (years)		51(43-64)	55(46-66)	53(46-65)
Age (years)	20-49	285（25.4）	487（38.6）	772（32.4）	54.638	<0.001
	50-79	839（74.6）	775（61.4）	1 614（67.6）
Race	White	817（72.7）	920（72.9）	1 737（72.8）	14.547	0.003
	Black	232（20.6）	237（18.8）	469（19.7）
	Other	75（6.7）	105（8.3）	180（7.5）
Marital status	Married	695（61.8）	776（61.5）	1 471（61.7）	2.531	0.089
	Not married	429（38.2）	486（38.5）	915（38.3）
Laterality	Left	572（50.9）	629（49.8）	1 201（50.3）	3.015	0.078
	Right	552（49.1）	633（50.2）	1 185（49.7）
Histologic grade	Ⅰ	34（3.0）	23（1.8）	57（2.4）	25.413	<0.001
	Ⅱ	209（18.5）	201（15.9）	410（17.1）
	Ⅲ	883（78.5）	1 038（82.3）	1 921（80.5）
AJCC stage	Ⅰ	595（52.9）	367（29.1）	962（40.3）	15.582	<0.001
	Ⅱ	471（41.9）	668（52.9）	1 139（47.7）
	Ⅲ	58（5.2）	227（18.0）	285（12.0）
Tumor diameter (cm)	≤2	661（58.8）	452（35.8）	1 113（46.6）	30.769	<0.001
	>2 & ≤5	425（37.8）	637（50.5）	1 062（44.5）
	>5	38（3.4）	173（13.7）	211（8.9）
Nodal status	0	875（77.8）	729（57.8）	1 604（67.2）	19.464	<0.001
	1-3	191（17.0）	349（27.6）	540（22.7）
	4-9	37（3.3）	106（8.4）	143（6.0）
	>9	21（1.9）	78（6.2）	99（4.1）
Radiation	Yes	1 124（100）	380（30.1）
	No	0	882（69.9）

Characteristics	Before matching（BCS+RT vs. Mastectomy）	After matching（BCS+RT vs. Mastectomy）
Age≥50 (years)	SMD=0.32（P<0.001）	SMD=0.05（P=0.21）
Tumor diameter≤2 cm	SMD=0.45（P<0.001）	SMD=0.03（P=0.67）
No lymph node metastasis	SMD=0.41（P<0.001）	SMD=0.02（P=0.83）
AJCC stage Ⅰ	SMD=0.51（P<0.001）	SMD=0.04（P=0.35）
Histologic grade Ⅰ+Ⅱ	SMD=0.12（P<0.001）	SMD=0.06（P=0.17）

Characteristics		BCSS			OS
Characteristics		HRs(95%CI)	χ² value	P value	HRs(95%CI)	χ² value	P value
Age(years)	20-49	1.098(0.92-1.243)	0.986	0.325	0.917(0.894-1.215)	1.054	0.618
Age(years)	50-79	1			1
Race	White	1			1
	Black	1.314(1.121-1.468)	4.763	0.029	1.295(1.097-1.474)	5.449	0.007
	Other	0.857(0.682-1.218)	1.674	0.381	0.916(0.753-1.187)	2.018	0.427
Marital status	Married	1			1
Marital status	Not married	1.361(1.172-1.624)	5.298	<0.001	1.357(1.286-1.687)	6.452	<0.001
Laterality	Left	1			1
Laterality	Right	0.937(0.788-1.146)	0.631	0.356	0.973(0.849-1.126)	0.831	0.653
Histologic grade	Ⅰ	0.207(0.076-0.631)	7.263	0.005	0.176(0.058-0.521)	9.527	0.003
	Ⅱ	0.706(0.535-0.876)	10.539	0.002	0.743(0.582-0.841)	12.246	0.002
	Ⅲ	1			1
AJCC stage	Ⅰ	0.305(0.243-0.382)	25.746	<0.001	0.339(0.264-0.479)	20.369	<0.001
	Ⅱ	1			1
	Ⅲ	3.49(3.103-4.528)	17.347	<0.001	3.504(3.107-4.325)	11.367	<0.001
Tumor diameter (cm)	≤2	1			1
	>2 & ≤5	2.968(2.405-3.367)	9.488	<0.001	2.591(2.253-3.207)	7.218	<0.001
	>5	7.946(6.435-9.825)	11.472	<0.001	7.189(5.944-8.892	10.375	<0.001
Nodal status	0	1			1
	1-3	3.109(2.348-3.673)	17.422	<0.001	2.591(2.327-3.246)	24.462	<0.001
	4-9	6.063(4.981-7.762)	9.871	<0.001	5.467(4.326-6.576)	13.225	<0.001
	>9	12.684(10.126-15.837)	12.026	<0.001	11.769(9.462-14.737)	8.773	<0.001
Type of surgery	BCS+RT	0.416(0.298-0.504)	5.437	<0.001	0.385(0.306-0.421)	7.468	<0.001
Type of surgery	Mastectomy	1		<0.001	1		<0.001

Characteristics		BCSS			OS
Characteristics		HR(95%CI)	χ² value	P value	HR(95%CI)	χ² value	P value
Race	White	1			1
	Black	1.036(0.854-1.273)	0.954	0.864	1.121(0.903-1.305)	1.125	0.627
	Other	0.874(0.593-1.175)	2.037	0.208	0.838(0.647-1.215)	0.693	0.251
Marital status	Married	1			1
Marital status	Not married	1.247(1.203-1.401)	13.261	0.014	1.312(1.136-1.509)	19.248	<0.001
Histologic grade	Ⅰ	0.347(0.125-1.046)	5.137	0.058	0.273(0.089-0.831)	8.934	0.024
	Ⅱ	0.904(0.670-1.127)	3.007	0.258	0.879(0.742-1.108)	2.763	0.257
	Ⅲ	1			1
AJCC stage	Ⅰ	1			1
	Ⅱ	0.716(0.489-1.128)	2.552	0.083	0.826(0.593-1.147)	1.931	0.194
	Ⅲ	0.824(0.591-1.206)	3.167	0.243	0.882(0.614-1.231)	0.678	0.307
Tumor diameter (cm)	≤2	1			1
	>2 & ≤5	1.617(1.179-2.153)	9.436	0.004	1.568(1.216-2.107)	13.772	0.003
	>5	3.285(2.367-4.621)	13.413	<0.001	3.011(2.146-3.979)	18.537	<0.001
Nodal status	0	1			1
	1-3	2.264(1.671-2.719)	26.248	<0.001	1.982(1.587-2.436)	29.553	<0.001
	4-9	4.419(2.738-6.874)	19.267	<0.001	3.735(2.583-5.889)	24.339	<0.001
	>9	8.018(5.327-12.997)	20.514	<0.001	7.864(5.149-11.837)	16762	<0.001
Type of surgery	BCS+RT	0.682(0.516-0.748)	8.537	<0.001	0.607(0.457-0.705)	7.651	<0.001
Type of surgery	Mastectomy	1			1

Characteristics	BCSS			OS
Characteristics	HR (95%CI）	χ² value	P value	HR (95%CI)	χ² value	P value
Age(years)
20-49	0.725(0.524-0.997)	0.841	0.038	0.806(0.569-1.117)	1.437	0.079
50-79	0.531(0.424-0.697)	37.953	<0.001	0.493(0.402-0.615)	36.218	<0.001
Histologic grade
Ⅰ	0.536(0.038-7.957)	1.256	0.687	0.543(0.036-8.107)	0.935	0.682
Ⅱ	0.584(0.329-0.985）	2.992	0.043	0.573(0.312-0.837)	5.436	0.015
Ⅲ	0.591(0.490-0.736)	17.638	<0.001	0.562(0.466-0.679)	19.379	<0.001
AJCC stage
Ⅰ	0.751(0.473-1.207)	1.357	0.225	0.749(0.508-1.114)	1.576	0.157
Ⅱ	0.607(0.483-0.809)	6.41	<0.001	0.562(0.463-0.714)	9.738	<0.001
Ⅲ	0.529(0.348-0.752)	10.379	<0.001	0.487(0.338-0.691)	8.337	<0.001
Tumor diameter(cm)
≤2	0.728(0.495-1.037)	2.965	0.071	0.702(0.516-0.937)	5.728	0.023
>2 & ≤5	0.571(0.484-0.775)	13.476	<0.001	0.531(0.418-0.660)	17.339	<0.001
>5	0.564(0.347-0.941)	5.816	0.031	0.554(0.328-0.898)	7.834	0.017
Nodal status
0	0.704(0.553-0.916）	5.437	0.012	0.614(0.488-0.801)	9.714	<0.001
1-3	0.579(0.406-0.757)	18.736	<0.001	0.533(0.374-0.719)	24.291	<0.001
4-9	0.587(0.346-0.982)	4.028	0.044	0.528(0.336-0.890)	6.229	0.015
>9	0.485(0.263-0.897)	9.517	0.021	0.457(0.251-0.844)	13.737	0.008