Treating brain metastases in metastatic breast cancer: outcomes after stereotactic radiosurgery examined in a retrospective, single-center cohort analysis

Figures & data

Table 1. Baseline characteristics at the time of SRS.

Baseline characteristics
	Total		ER+/HER2+		ER+/HER2		ER−/HER2+		ER−/HER2
	n	(%)	n	(%)	n	(%)	n	(%)	n	(%)
No. of patients	149	(100)	39	(26)	49	(33)	37	(25)	23	(15)
Time from BC diagnosis to BM
Median, months (range)	51 (1–346)		65 (7–272)		91 (2–346)		34 (1–112)		30 (1–175)
Histology
IDC	131	(88)	32	(82)	43	(88)	33	(89)	22	(96)
ILC	6	(4)	2	(5)	3	(6)	1	(3)	0	(0)
Other	12	(8)	5	(13)	3	(6)	3	(8)	1	(4)
Metastases
Bone	75	(50)	24	(62)	33	(67)	10	(27)	8	(35)
Lung	60	(40)	17	(44)	22	(45)	11	(30)	9	(39)
Liver	56	(38)	13	(33)	23	(47)	13	(35)	7	(30)
Lines of treatment
Median (range)	4 (1–13)		5(1–11)		5(1–13)		3(1–11)		3(1–7)
1–2 lines	42	(28)	8	(21)	13	(26)	14	(38)	6	(26)
3–5 lines	56	(38)	15	(38)	16	(33)	12	(32)	13	(57)
6+ lines	51	(34)	16	(41)	20	(41)	11	(30)	4	(17)
Treatment prior to SRS
Endocrine therapy	73	(49)	25	(64)	40	(82)	7	(19)	1	(4)
HER2−targeted treatment	76	(51)	34	(87)	7	(14)	33	(89)	2	(9)
Chemotherapy	110	(74)	32	(82)	34	(69)	29	(78)	15	(65)

BC: breast cancer; BM: brain metastases; IDC: invasive ductal carcinoma; ILC: invasive lobular carcinoma; SRS: stereotactic radiosurgery; HER2: human epidermal growth factor receptor 2.

Table 2. Radiotherapy characteristics at time of SRS.

Radiotherapy characteristics
	Total		ER+/HER2+		ER+/HER2		ER−/HER2+		ER−/HER2
	n	(%)	n	(%)	n	(%)	n	(%)	n	(%)
No. of patients	149	(100)	39	(26)	49	(33)	37	(25)	23	(15)
Age at time of SRS in years
Median (range)	59 (25–91)		53 (25–80)		65 (29–82)		58 (36–81)		58 (33–91)
Total number of lesions	267		73		85		70		38
Type of SRS
Single-fraction	97	(65)	16	(41)	36	(73)	25	(68)	19	(83)
FSRS	52	(35)	23	(59)	13	(27)	12	(32)	4	(17)
No. of treated BM
Median (range)	1 (1–6)		1 (1–4)		1 (1–5)		2 (1–6)		1 (1–4)
WBI prior to SRS	25	(17)	9	(23)	5	(10)	9	(24)	2	(9)
Total volume of treated metastases in cm^3
Median	3.73		2.84		2.6		5.56		5.38
(range)	(0.04–59.25)		(0.13–59.25)		(0.04–38.11)		(0.04–47.76)		(0.09–36.67)
1st quartile	0.92		0.68		0.58		1.44		2.83
3rd quartile	10.66		5.45		9.53		12.46		14.52

SRS: stereotactic radiosurgery; FSRS: fractionated stereotactic radiosurgery; BM: brain metastases; WBI: whole brain irradiation.

Figure 1. Kaplan–Meier Curves for OS by (a) receptor profiles, (b) HER2 status, (c) lines of treatment dichotomized at the median (four lines), and (d) presence of extracranial visceral metastases yes/no.

Table 3. Univariate and multivariate Cox regression analysis for OS.

Univariate and multivariate Cox regression analysis for OS
Prognostic factor	Univariate analysis Hazard ratio (95% CI) p value	Multivariate analysis Hazard ratio (95% CI) p value
ER+/HER2−	1.00	1.00
ER+/HER2+
<12 months after SRS	0.73 (0.39–1.39) .34
≥12 months after SRS	0.36 (0.17–0.78) .009	0.43 (0.19–0.96)** .04
ER−/HER2+	0.68 (0.43–1.09) .11
ER−/HER2−	2.19 (1.30–3.71) .003	2.00 (1.09–3.67)*** .02
ER positive vs. negative	0.78 (0.55–1.12) .18
HER2 positive vs. negative	0.50 (0.35–0.71) .0001*
Age (>59 vs. ≤59)	1.92 (1.34–2.73) .0003	1.23 (0.70–2.14)*** .47
Lines of treatment (>4 vs. ≤4)
<12 months after SRS	1.24 (0.74–2.06) .41
≥12 months after SRS	0.55 (0.33–0.91) .02	0.40 (0.20–0.82)*** .01
Presence of extracranial visceral metastases yes vs. no	1.72 (1.20–2.47) .003	2.90 (1.53–5.50)*** .001
Time from BC diagnosis to BCBM (>57 vs. ≤57 months)	1.05 (0.74–1.48) .79
WBI before SRS yes vs. no	1.07 (0.68–1.68) .78
Treated tumor volume (>3.73 cm^3 vs. ≤3.73)	0.90 (0.64–1.27) .55
No. of treated lesions (>1 vs. 1)	0.95 (0.67–1.35) .78

Bold p value = statistically significant (p < .1 in univariate analysis, p < .05 in multivariate analysis).

OS: overall survival; CI: confidence interval; ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; SRS: stereotactic radiosurgery; BC: breast cancer; BCBM: breast cancer brain metastases; WBI: whole brain irradiation.

*HER2 status, although significant in univariate analysis, was excluded from the multivariate model, as HER2 as a factor was already accounted for via the four receptor subtypes.

**MVA model including: ER+/HER2+ ≥12 months, age, lines of treatment ≥12 months, and presence of extracranial visceral metastases.

***MVA model including: ER−/HER2−, age, lines of treatment ≥12 months, and presence of extracranial visceral metastases.

Figure 2. Cumulative incidence for CNS-PFS illustrated for the entire cohort.

Figure 3. Cumulative incidence for CNS-PFS illustrated by presence of extracranial visceral metastases Yes/no.

Table 4. Univariate and multivariate Fine-Gray regression analysis for CNS-PF.

Univariate and multivariate Fine-Gray regression analysis for CNS-PFS
Prognostic factor	Univariate analysis SHR (95% CI) p value	Multivariate analysis SHR (95% CI) p value
ER+/HER2−	1.00	1.00
ER+/HER2+
<12 months after SRS	2.44 (0.96–6.21) .06	1.58 (0.57–4.42)** .27
≥12 months after SRS	0.86 (0.45–1.63) .63
ER−/HER2+	1.30 (0.76–2.20) .34
ER−/HER2−	1.03 (0.53–1.98) .93
ER positive vs. negative	0.89 (0.59–1.33) .56
HER2 positive vs. negative
<12 months after SRS	2.43 (0.99–6.00) .05*
≥12 months after SRS	1.00 (0.63–1.58) .99
Age (>59 vs. ≤59)
<12 months after SRS	0.38 (0.16–0.92) .03	0.56 (0.20–1.57)** .38
≥12 months after SRS	0.68 (0.43–1.08) .10
Lines of treatment (>4 vs. ≤4)
<12 months after SRS	4.54 (1.77–11.62) .002	2.88 (1.06–7.81)** .04
≥12 months after SRS	1.15 (0.73–1.82) .54
Presence of extracranial visceral metastases yes vs. no	0.71 (0.47–1.06) .095	0.54 (0.30–0.97)** .04
Time from BC diagnosis to BCBM (>57 vs. ≤57 months)
<12 months after SRS	0.91 (0.39–2.11) .83
≥12 months after SRS	0.64 (0.40–1.01) .06	0.68 (0.43–1.10)*** .12
WBI before SRS yes vs. no	0.96 (0.56–1.64) .87
Treated tumor volume (>3.73 cm^3 vs. ≤3.73 cm^3)	1.34 (0.90–2.01) .15
No. of treated lesions (>1 vs. 1)	1.31 (0.88–1.95) .19

Bold p value = statistically significant (p < .1 in univariate analysis, p < .05 in multivariate analysis).

CNS-PFS: central nervous system progression-free survival; SHR: sub-distributional hazard ratio; CI: confidence interval; ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; SRS: stereotactic radiosurgery; BC: breast cancer; BCBM: breast cancer brain metastases; WBI: whole brain irradiation.

*HER2 status, although significant in univariate analysis, was excluded from the multivariate model, as HER2 as a factor was already accounted for via the four receptor subtypes.

**MVA model including: ER+/HER2+ under 12 months, age <12 months, lines of treatment <12 months, and presence of extracranial visceral metastases.

***MVA model including: Time from BC diagnosis to BCBM ≥12 months after SRS and presence of extracranial visceral metastases.

Data availability statement

The data supporting the findings of this study are not publicly available due to institutional restrictions. The data can be made available to qualified researchers through application to the Danish Breast Cancer Group.