Predictors of recurrence in breast cancer patients with pathological partial response

Trabulus, Fadime Didem Can; Nazli, Mehmet Ali; Arslan, Esra; Mermut, Ozlem; Dal, Fatih; Akce, Bulent; Gursu, Riza Umar; Talu, Esra Canan Kelten; Couteau, Jacqueline Nur Adira

doi:10.1590/1806-9282.20231215

Fadime Didem Can Trabulus ^**Corresponding author: didemcan73@gmail.com

Conceptualization

Data curation

Formal Analysis

Methodology

Resources

Visualization

Writing – original draft

Writing – review & editing

Bahçeşehir University, School of Medicine, Goztepe Medical Park Hospital, Department of General Surgery – İstanbul, Turkey.

http://orcid.org/0000-0003-1687-715X

Mehmet Ali Nazli

Conceptualization

Methodology

Writing – original draft

Writing – review & editing

University of Health Sciences, Istanbul Training and Education Hospital, Department of Radiology – İstanbul, Turkey.

http://orcid.org/0000-0003-4605-7822

Esra Arslan

Conceptualization

Data curation

Writing – original draft

Writing – review & editing

University of Health Sciences, Istanbul Training and Education Hospital, Department of Nuclear Medicine – İstanbul, Turkey.

http://orcid.org/0000-0002-9222-8883

Ozlem Mermut

Conceptualization

Data curation

Methodology

Writing – review & editing

University of Health Sciences, Istanbul Training and Education Hospital, Department of Radiation Oncology – İstanbul, Turkey.

http://orcid.org/0000-0002-5449-7361

Fatih Dal

Conceptualization

Formal Analysis

Writing – original draft

University of Health Sciences, Istanbul Training and Education Hospital, Department of General Surgery – İstanbul, Turkey.

http://orcid.org/0000-0002-9768-8125

Bulent Akce

Conceptualization

Writing – review & editing

University of Health Sciences, Istanbul Training and Education Hospital, Department of General Surgery – İstanbul, Turkey.

http://orcid.org/0000-0002-0275-1882

Riza Umar Gursu

Data curation

Methodology

Visualization

University of Health Sciences, Istanbul Training and Education Hospital, Department of Medical Oncology – İstanbul, Turkey.

http://orcid.org/0000-0002-6331-3632

Esra Canan Kelten Talu

Data curation

Writing – review & editing

University of Health Sciences, İzmir Faculty of Medicine, Department of Pathology – İzmir, Turkey.

http://orcid.org/0000-0001-8767-4275

Jacqueline Nur Adira Couteau

Writing – review & editing

Bahçeşehir University, School of Medicine – İstanbul, Turkey.

http://orcid.org/0009-0000-9584-9266

*Corresponding author: didemcan73@gmail.com

Conflicts of interest: the authors declare there is no conflicts of interest.

Features	Category	Patients n=151 (%)
Age (years)	<50	67(44.4)
Age (years)	≥50	84(55.6)
cT stage	I–II	111(73.5)
cT stage	III–IV	40(26.5)
cN stage	0–I	130(86.1)
cN stage	II–III	21(13.9)
Histological type	Invasive ductal carcinoma	126(83.4)
Histological type	Others	25(16.6)
Surgical type	Breast-conserving surgery	61(40.4)
Surgical type	Mastectomy	90(59.6)
Tumor grade	I–II	106(70.2)
Tumor grade	III	45(29.8)
Lymphovascular invasion	Positive	65(43.0)
In situ carcinoma	Yes	92(60.9)
ypT stage	I	101(66.9)
	II	37(24.5)
	III	13(8.6)
Lymph node invasion	Positive	100(66.2)
Estrogen receptor	Positive	115(76.2)
Progesterone receptor	Positive	96(63.6)
HER2	Positive	33(21.9)
Ki-67	<20%	26(17.2)
Ki-67	≥20%	125(82.8)
Molecular subtype	Luminal-A	15(9.9)
	Luminal B/HER2(–)	85(56.3)
	Luminal B/HER2(+)	17(11.3)
	Non-luminal B/HER2(+)	16(10.6)
	Triple-negative	18(11.9)
Molecular subtype	Luminal	117(77.5)
Molecular subtype	Non-luminal	34(22.5)
Loco-regional recurrence	Breast	0(0.0)
	Thorax wall	6(4.0)
	Axilla	1(0.7)
Systemic recurrence	Yes	20(13.2)

Factors	Category	LRRFS (92.8%)	p	DFS (73.8%)	p	DSS (83.1%)	p
Age (years)	<50	91.3	0.485	78.3	0.449	91.2	0.290
Age (years)	≥50	94.0	0.485	70.2	0.449	84.6	0.290
cT stage	I–II	93.4	0.932	70.7	0.509	83.7	0.321
cT stage	III–IV	90.5	0.932	82.0	0.509	85.9	0.321
cN stage	0–I	94.3	0.326	75.6	0.421	88.9	0.005^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.
cN stage	II–III	85.5	0.326	65.0	0.421	69.3
Histological type	Invasive ductal carcinoma	93.0	0.978	71.8	0.447	81.3	0.219
Histological type	Others	91.7	0.978	88.0	0.447	100.0	0.219
Surgical type	Breast-conserving surgery	100.0	0.040^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	86.8	0.044^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	96.9	0.108
Surgical type	Mastectomy	88.9		66.8		77.7	0.108
Tumor grade	I–II	100.0	<0.001^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	75.6	0.033^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	83.9	0.351
Tumor grade	III	78.4		55.2		79.8	0.351
Lymphovascular invasion	Positive	85.9	0.018^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	53.9	<0.001^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	62.6	<0.001^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.
Lymphovascular invasion	Negative	97.9		89.1		100.0
In situ carcinoma	Yes	91.4	0.546	61.5	0.005^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	74.3	0.012^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.
In situ carcinoma	No	94.9	0.546	94.9		100.0
pT stage	I–II	92.8	0.754	77.0	0.007^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	86.8	0.034^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.
pT stage	III	91.7	0.754	53.3		77.1
Lymph node invasion	Yes	89.4	0.058	68.5	0.021^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	75.1	0.024^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.
Lymph node invasion	No	100.0	0.058	82.6		100.0
Estrogen receptor	Positive	97.3	0.002^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	73.5	0.235	83.1	0.325
Estrogen receptor	Negative	78.8		70.1	0.235	81.4	0.325
Progesterone receptor	Positive	98.7	0.005^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	74.5	0.169	82.0	0.444
Progesterone receptor	Negative	82.4		71.1	0.169	83.0	0.444
HER2	Positive	81.7	0.003^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	77.7	0.590	93.0	0.567
HER2	Negative	96.5		71.7	0.590	78.8	0.567
Ki-67	<20%	100.0	0.239	87.5	0.110	100.0	0.659
Ki-67	≥20%	91.5	0.239	71.4	0.110	88.2	0.659
Molecular subtype	Luminal-A	100.0	0.002^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	83.3	0.507	100.0	0.637
	Luminal B/HER2(–)	98.5		75.2		81.0
	Luminal B/HER2(+)	91.7		91.7		100.0
	Non-luminal B/HER2(+)	71.3		63.2		85.7
	Triple-negative	80.0		72.9		68.6
Molecular subtype	Luminal	97.3	0.001^* * p<0.05, p-value given refer to log-rank test. DFS: disease-free survival; DSS: disease specific survival; LRRFS: locoregional recurrence free survival.	74.3	0.153	83.4	0.259
Molecular subtype	Non-luminal	77.4		67.8	0.153	80.1	0.259

Factors	Category	Loco-regional recurrence-free survival HR (95%CI)	p-value	Disease-free survival HR (95%CI)	p-value	Disease-specific survival HR (95%CI)	p-value
Age (years)	<50	3.55(0.44–28.94)	0.237	Reference (1)	0.617	Reference (1)	0.125
Age (years)	≥50	Reference (1)	0.237	1.30(0.46–3.65)	0.617	3.41(0.71–16.34)	0.125
cT stage	I–II	Reference (1)	0.135	Reference (1)	0.003^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	Reference (1)	0.358
cT stage	III–IV	5.65(0.58–54.88)	0.135	5.66(1.77–18.09)		2.06(0.44–9.62)	0.358
cN stage	0–I	Reference (1)	0.791	Reference (1)	0.803	Reference (1)	0.025^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.
cN stage	II–III	1.34(0.15–11.87)	0.791	1.14(0.40–3.27)	0.803	5.14(1.22–21.59)
Histological type	Invasive ductal carcinoma	Reference (1)	0.237	Reference (1)	0.607	Reference (1)
Histological type	Others	5.66(0.39–82.06)	0.237	1.49(0.32–6.88)	0.607	^ As there is no event, it is not included in Cox regression modeling.
Surgery	Breast-conserving surgery	Reference (1)		Reference (1)	0.444	Reference (1)	0.200
Surgery	Mastectomy	^ As there is no event, it is not included in Cox regression modeling.		1.67(0.45–6.17)	0.444	4.23(0.47–38.44)	0.200
Tumor grade	I–II	Reference (1)		Reference (1)	0.180	Reference (1)	0.941
Tumor grade	III	^ As there is no event, it is not included in Cox regression modeling.		2.02(0.72–5.64)	0.180	1.06(0.24–4.68)	0.941
Lymphovascular invasion	Positive	22.35(1.42–352.62)	0.027^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	4.35(1.18–15.94)	0.027^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	^ As there is no event, it is not included in Cox regression modeling.
Lymphovascular invasion	Negative	Reference (1)		Reference (1)		Reference (1)
In situ carcinoma	Yes	1.04(0.15–6.98)	0.972	7.37(1.52–35.71)	0.013^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	^ As there is no event, it is not included in Cox regression modeling.
In situ carcinoma	No	Reference (1)	0.972	Reference (1)		Reference (1)
pT stage	I–II	Reference (1)	0.499	Reference (1)	0.004^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	Reference (1)	0.089
pT stage	III	2.58(0.17–40.34)	0.499	5.42(1.69–17.35)		3.87(0.81–18.45)	0.089
Lymph node invasion	Yes	^ As there is no event, it is not included in Cox regression modeling.		3.70(0.77–17.87)	0.103	^ As there is no event, it is not included in Cox regression modeling.
Lymph node invasion	No	Reference (1)		Reference (1)	0.103	Reference (1)
Molecular subtype	Luminal	Reference (1)	0.003^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	Reference (1)	0.015^* * p<0.05; hazard ratio (HR) is presented with their 95% confidence interval (CI) and p-value.	Reference (1)	0.233
Molecular subtype	Non-luminal	27.34(2.99–249.14)		4.41(1.33–14.58)		2.75(0.52–14.55)	0.233

Factors	Category	DFS (67.8%)	p	DSS (75.8%)	p
Number of metastatic lymph nodes	1–3	81.0	0.025^* * p<0.05, p-values given refer to log-rank test. DFS: disease-free survival; DSS: disease-specific survival; ITC: isolated tumor cells.	92.1
	4–9	70.4		81.8
	≥10	46.7		62.5	0.453
Size of metastasis	ITC and micrometastasis	79.1	0.421	90.0
Size of metastasis	Macrometastasis	65.3	0.421	73.4	0.603
Extra nodal extension	Yes	62.5	0.385	68.0
Extra nodal extension	No	76.5	0.385	93.8	0.148

[1] *Corresponding author: didemcan73@gmail.com

Brasil

Brasil

Predictors of recurrence in breast cancer patients with pathological partial response

SUMMARY

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION: