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BMC Cancer

, 19:26 | Cite as

Clinicopathological features, treatment patterns, and prognosis of squamous cell carcinoma of the breast: an NCDB analysis

  • Liling ZhuEmail author
  • Kai ChenEmail author
Open Access
Research article
  • 286 Downloads
Part of the following topical collections:
  1. Surgical oncology and imaging

Abstract

Background

Squamous cell carcinoma (SCC) of the breast is a rare malignancy. The clinicopathological features, treatment patterns and prognosis of SCC of the breast is still unclear.

Methods

In this study, we performed a 1:4 SCC-IDC (infiltrating ductal carcinoma) matching analysis of patients diagnosed between 2004 and 2014, using the data from the national cancer database. We used Chi-square test to compare the clinicopathological features and treatment patterns between SCC (n = 686) and IDC (n = 2744) patients. We used Kaplan-Meier analysis and Cox-regression to estimate the survival of SCC and IDC patients.

Results

We observed that SCC patients are more likely to have T3–4, grade III, and ER negative diseases, when compared to IDC patients. Breast conserving surgery (BCS) (58.3% vs 65.4%, p = 0.048), as well as radiotherapy after BCS (65.3% vs. 83.0%, p < 0.001), was less performed in SCC patients. Among low-risk patients, chemotherapy was used more often for SCC patients (42.9%) than for IDC (18.7%) patients (p = 0.002). In HR-positive patients, endocrine therapy was used less often for SCC patients (51.6%) than for IDC patients (70.5%) (p < 0.001). SCC (vs. IDC) was associated with no responses to neoadjuvant chemotherapy (20% vs. 5.05%, p = 0.019). Adjusted analysis confirmed that SCC (vs. IDC) was associated with worse OS (HR = 1.40, 95%CI 1.17–1.67, P < 0.01), after a median follow-up of 58.3 months. In SCC patients, HR status is not prognostic of OS, but endocrine therapy was significantly associated with improved OS in HR-positive SCC patients.

Conclusions

We conclude that SCC is associated with poorer clinicopathological features, no responses to neoadjuvant chemotherapy and worse clinical outcomes than IDC. The treatment patterns for SCC and IDC are different. Endocrine therapy is necessary for HR-positive SCC patients.

Keywords

Breast cancer Squamous cell carcinoma Infiltrating ductal carcinoma Survival Endocrine therapy Chemotherapy 

Abbreviations

BCS

Breast-conserving surgery

ER

Estrogen receptor

HR

Hormonal receptor

IDC

Infiltrating ductal carcinoma

LN

Lymph node

LVI

Lymphovascular invasion

NCDB

National cancer database

OS

Overall survival

PR

Progesterone receptor

RT

Radiation therapy

SCC

Squamous cell carcinoma

Background

Squamous cell carcinoma (SCC) of the breast is a rare malignancy that accounts for < 0.2% of all breast cancers [1]. Diagnosis of SCC can be made when a predominance (> 90%) of areas with squamous cells is noticed at histology examinations [2]. The origin of the SCC component is still an unanswered question. A recent study [3] showed that SCC and its adjacent infiltrating ductal carcinoma (IDC) component shared the same origin, but their transcription landscape [4] and driven-pathways [5] are different. Thus, whether the differing histology of SCC may result in different biological behavior, different treatment patterns and prognosis is not clear. Most of the studies [1, 6] are limited significantly by their small sample size, due to its rarity. Therefore, a national cancer database remains as the only choice to provide adequate sample size to investigate SCC of the breast.

The national cancer database (NCDB) is a hospital-based database that covers approximately 70% of cancer patients in the United States [7]. The participating centers are required to submit data to the database. In this study, we used the NCDB to compare the clinicopathological features, treatment patterns and prognoses of IDC and SCC patients. We hypothesized that SCC (vs. IDC) was associated with poor clinicopathological characteristics, different treatment patterns, and worse survival. We also performed an exploratory analysis of the benefits of systemic therapies for SCC patients.

Methods

We searched the NCDB for eligible patients using the inclusion and exclusion criteria below:

Inclusion

  1. 1)

    Female patients with pathologically confirmed breast cancer,

     
  2. 2)

    Patients who were diagnosed between 2004 and 2014, and

     
  3. 3)

    Diagnoses of SCC of the breast (code 8070–8078), and IDC (code 8500).

     

Exclusion criteria

  1. 1)

    Patients with prior diagnoses of malignant tumors and

     
  2. 2)

    A number of follow-up months equal to 0.

     

A total of 686 SCC patients and 1,211,403 IDC patients were identified from the database. Given the huge discrepancy of the amount of the SCC and IDC patients, we performed a 1:4 SCC-IDC matching on the following factors: Year of diagnosis (2004–2014), Facility type (Community Cancer Program, Comprehensive Community Cancer Program, Academic/Research Program, Integrated Network Cancer Program, Unknown), Facility location (New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West North Central, West South Central, Mountain, Pacific), city type (Metropolitan, Non-metropolitan/Unknown), type of insurance (Not insured, Private insurance, Medicaid, Medicare, other Government, Unknown.). There were 686 SCC and 2744 IDC patients being selected as the final cohort for analysis. This study was an epidemiological study using de-identified data from the NCDB database. Therefore, consent for patient participation and study publication was not required. The study approval was waived by the ethical committee of Yale University and Sun Yat-sen Memorial Hospital.

The following data were collected for each patient: the year of diagnosis, age, race, Charlson-Deyo score, tumor grade, lymphovascular invasion, T-stage, N-stage, histology, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, primary surgery categorization, radiation therapy (RT), chemotherapy, neoadjuvant chemotherapy, response to chemotherapy, endocrine therapy, survival month and OS status. Patients were categorized into three age groups based on their ages at diagnosis (≤50 yrs., 50–60 yrs., > 60 yrs). We used this cut-off because the median age was close to 60 yrs. in our study population and because 50 yrs. is the usual cut-off age for premenopausal and post-menopausal women. Histology was divided into two categories, namely, IDC and SCC.

Statistical analysis

We conducted a descriptive analysis of the baseline clinicopathological features of the included patients and used the Chi-square test to compare the characteristics of the patients with different histologies. The median follow-up time was calculated as the median observed survival time of the entire population. OS was measured as the time from diagnosis to death due to any cause. The cumulative OS rates were estimated using Kaplan-Meier analysis. We used a Cox regression model to screen for prognostic factors of OS. We tested the proportional hazards assumption by plotting the scaled Schoenfeld residuals of all coefficients over time and found no violations. All P-values were two-sided. P-values less than 0.05 were considered statistically significant. Statistical analysis was performed using Stata/MP, version 13.0 (StataCorp LP, College Station, TX, USA).

Results

A total of 3430 patients (IDC: 2744; SCC: 686), with a median age of 61 years, were included in this study. The clinicopathological features are listed in Table 1. In general, SCC is associated with poorer clinicopathological features. A total of 23.1% of the SCC patients had T3–4 disease, whereas only 4% of the IDC patients had T3–4 disease. The proportions of grade III disease were 61.06 and 39.10% for the SCC and IDC patients, respectively. Additionally, the proportions of ER-negative tumors were 74.91 and 21.95% for the SCC and IDC patients, respectively. The distribution of N-stage was similar between SCC and IDC patients.
Table 1

Clinicopathological features of study population

 

Histology

P

Infiltrating Ductal Carcinoma

Squamous Cell Carcinoma

N

%a

N

%a

Race

 White

2259

83.33

540

79.65

< 0.01

 African American

343

12.65

119

17.55

 Others

109

4.02

19

2.80

 Unknown

33

 

8

  

Charlson-Deyo Score

 0

2346

85.50

555

80.90

0.02

 1

328

11.95

104

15.16

 2

54

1.97

20

2.92

 3

16

0.58

7

1.02

Grade

 I

476

18.90

62

11.33

< 0.01

 II

1058

42.00

151

27.61

 III

985

39.10

334

61.06

 Unknown/IV

225

 

139

  

Lymphovascular Invasion

 Absence

768

79.67

185

85.65

0.04

 Present

196

20.33

31

14.35

 Not Applicable

1780

 

470

  

T-Stage

 T0-T1

1441

52.51

145

21.14

< 0.01

 T2

502

18.29

178

25.95

 T3

67

2.44

100

14.58

 T4

45

1.64

58

8.45

 Tx

689

25.11

205

29.88

N-Stage

 N0

1373

50.04

331

48.25

0.228

 N1

381

13.88

85

12.39

 N2

115

4.19

22

3.21

 N3

56

2.04

16

2.33

 Nx

819

29.85

232

33.82

M-Stage

 M0

2250

82.00

490

71.43

< 0.01

 M1

49

1.79

23

3.35

 Mx

445

16.22

173

25.22

Estrogen Receptor

 Negative

569

21.95

421

74.91

< 0.01

 Positive

2023

78.05

141

25.09

 Unknown

152

 

124

  

Progesterone Receptor

 Negative

843

32.69

491

87.84

< 0.01

 Positive

1736

67.31

68

12.16

 Unknown

165

 

127

  

HER2b

 Negative

829

78.2

207

87.7

< 0.01

 Borderline

31

2.9

2

0.9

 Positive

200

18.9

27

11.4

 Unknown

156

 

68

  

Breast Surgery

 No_Surgery

167

6.10

90

13.16

< 0.01

 Breast-conserving surgery

1561

56.99

246

35.96

 Mastectomy

1010

36.87

348

50.88

 Surgery (Types_Unknown)

1

0.04

0

0.00

 Unknown

5

 

2

  

Radiation Therapy

 No

1119

41.23

373

54.93

< 0.01

 Yes

1595

58.77

306

45.07

 Unknown

30

 

7

  

Chemotherapy

 None

1506

58.28

294

46.08

< 0.01

 Single-Agent Chemotherapy

44

1.70

23

3.61

 Multiagent Chemotherapy

1034

40.02

321

50.31

 Unknown

160

 

48

  

Neoadjuvant chemotherapy

 No

1884

89.89

447

83.86

< 0.01

 Yes

212

10.11

86

16.14

 Unknown

91

 

14

  

Endocrine Therapy

 No

1110

42.53

567

85.91

< 0.01

 Yes

1500

57.47

93

14.09

 Unknown

134

 

26

  

aPercentages were calculated based on the available data

bOnly patients after 2010 were used for analysis of HER2 status

Different treatment patterns between SCC and IDC patients

In patients with T1–2 stages who did not received neoadjuvant chemotherapy, there were 58.3% (120/206) vs. 65.4% (890/1362) of the SCC and IDC patients received BCS (P = 0.048) respectively. Among the patients with BCS (N = 1791, 16 patients with unknown RT status were excluded.), 65.3 and 83.0% of the SCC and IDC patients received RT (P < 0.01), respectively. The use of RT in node-positive patients with mastectomies, were similar in SCC and IDC patients (42.1% (37/88) vs. 48.4%(166/343), P = 0.287).

In patients with favorable prognosis (hormone receptor (HR)-positive, HER2-negative and node-negative), chemotherapy was performed in 42.9% (12/28) and 18.7% (80/427) of the SCC and IDC patients, respectively (P = 0.002). In the HR-positive, node-negative patients who were diagnosed before 2010 (when the HER2 status was unknown), there were 51.6% (32/62) and 24.9% (248/997) of the SCC and IDC patients who had received chemotherapy, respectively (P < 0.001). Among the patients with HR-positive disease, endocrine therapy was performed in 51.6% (79/153) and 70.5% (1446/2050) of the SCC and IDC patients, respectively (P < 0.001).

Response to neoadjuvant chemotherapy

In this study, there were 298 patients with known history of neoadjuvant chemotherapy, and 129 of them had clear information about treatment responses (CR, PR, CR/PR, No response). SCC (vs. IDC) was significantly associated with no responses to neoadjuvant chemotherapy (20% vs. 5.05%, P = 0.019) (Table 2).
Table 2

Response to neoadjuvant chemotherapy by histology

Category 1

 Histology

CR

PR, CR/PR

No response

Total

P*

N

%

N

%

N

%

N

%

 IDC

35

35.35

59

59.6

5

5.05

99

100

0.042

 SCC

8

26.67

16

53.33

6

20

30

100

Category 2

 Histology

Response (CR, PR, CR/PR)

No response

Total

P*

N

%

N

%

N

%

 IDC

94

94.95

5

5.05

99

100

0.019

 SCC

24

80

6

20

30

100

CR Complete Response, PR Partial Response, IDC Infiltrating Ductal Carcinoma, SCC Squamous Cell Carcinoma

*Fisher Exact test

Survival analysis

With a median follow-up time of 58.3 months, the respective 5-yr and 10-yr OS were 62.1 and 50.6% for the SCC patients, and 83.0 and 69.5% for the IDC patients, respectively (P < 0.001). SCC (vs. IDC) was associated with poorer OS in univariate analysis (HR = 2.39, 95%CI 2.06–2.77, P < 0.001), and in multivariate (HR = 1.40,95%CI 1.17–1.67, P < 0.001) analysis after adjusting for age, race, comorbidity, T-stage, N-stage, M-stage, ER, PR, tumor grade, LVI, surgery, endocrine therapy, chemotherapy and RT (Table 3, & Additional file 1: Figure S1). In patients who were diagnosed after 2010, SCC (vs. IDC) was still associated with poorer OS (HR = 1.57, 95%CI 1.11–2.21, P = 0.011), after adjusting for the above variables, as well as LVI and HER2 status.
Table 3

Univariate and multivariate analysis of prognostic factors of OS

Variables

Univariate analysis

Multivariate analysis

HR(95%CI)

P

HR(95%CI)

P

Age

  < =50

1

 

1

 

 50–60

1.13 (0.89–1.44)

0.301

1.10 (0.86–1.40)

0.445

  > 60

2.25 (1.86–2.74)

< 0.001

2.11 (1.72–2.60)

< 0.001

Race

 White

1

 

1

 

 African American

1.51 (1.26–1.80)

< 0.001

1.05 (0.87–1.27)

0.576

 Others

0.43 (0.24–0.77)

0.004

0.48 (0.27–0.85)

0.012

 Unknown

0.53 (0.24–1.19)

0.126

0.49 (0.22–1.10)

0.082

Comorbidity score

 Score 0

1

 

1

 

 Score 1

2.17 (1.85–2.54)

< 0.001

1.65 (1.40–1.95)

< 0.001

Grade

 I

1

 

1

 

 II

1.20 (0.94–1.54)

0.149

0.98 (0.76–1.26)

0.877

 III

2.05 (1.62–2.58)

< 0.001

1.35 (1.05–1.74)

0.02

 Unknown/IV

1.86 (1.39–2.49)

< 0.001

1.05 (0.77–1.42)

0.767

T-stage

 T0-T1

1

 

1

 

 T2

2.24 (1.86–2.69)

< 0.001

1.65 (1.35–2.03)

< 0.001

 T3–4

5.63 (4.60–6.90)

< 0.001

2.75 (2.14–3.55)

< 0.001

 Tx

1.25 (1.04–1.51)

0.017

0.62 (0.45–0.85)

0.003

N-stage

 N0

1

 

1

 

 N1

1.82 (1.49–2.22)

< 0.001

1.77 (1.43–2.18)

< 0.001

 N2–3

3.61 (2.90–4.49)

< 0.001

2.18 (1.69–2.83)

< 0.001

 Nx

1.12 (0.94–1.32)

0.197

0.95 (0.70–1.30)

0.764

M-stage

 M0

1

 

1

 

 M1

8.47 (6.42–11.17)

< 0.001

4.50 (3.29–6.16)

< 0.001

 Mx

2.04 (1.74–2.39)

< 0.001

1.90 (1.53–2.36)

< 0.001

Histology

 Infiltrating Ductal Carcinoma

1

 

1

 

 Squamous Cell Carcinoma

2.39 (2.06–2.77)

< 0.001

1.37 (1.15–1.64)

< 0.001

Lymphovascular invasiona

 Absence

1

 

Not included

 Presence

1.91 (1.37–2.67)

< 0.001

 Not applicable/Unknown

2.18 (1.63–2.91)

< 0.001

Estrogen Receptor

 Negative

1

 

1

 

 Positive

0.53 (0.46–0.61)

< 0.001

0.86 (0.67–1.10)

0.218

 Unknown

0.85 (0.67–1.08)

0.195

2.46 (0.60–10.15)

0.212

Progesterone Receptor

 Negative

1

 

1

 

 Positive

0.56 (0.48–0.65)

< 0.001

0.96 (0.76–1.20)

0.724

 Unknown

0.92 (0.73–1.16)

0.484

0.31 (0.08–1.27)

0.103

HER2a

 Negative

1

 

Not included

 Positive

0.83 (0.57–1.22)

0.347

 Borderline/Unknown

1.20 (0.87–1.66)

0.266

Surgery

 Breast-conserving surgery

1

 

1

 

 Mastectomy

2.22 (1.90–2.59)

< 0.001

1.26 (1.04–1.54)

0.02

 Others/Unknown

7.05 (5.77–8.62)

< 0.001

6.57 (5.04–8.55)

< 0.001

Radiation therapy

 No

1

 

1

 

 Yes

0.54 (0.47–0.62)

< 0.001

0.92 (0.77–1.10)

0.351

 Unknown

0.50 (0.24–1.05)

0.067

0.54 (0.25–1.17)

0.12

Chemotherapy

 No

1

 

1

 

 Yes

0.89 (0.77–1.03)

0.116

0.67 (0.55–0.80)

< 0.001

 Unknown

0.72 (0.53–0.99)

0.043

0.61 (0.43–0.85)

0.004

Endocrine therapy

 No

1

 

1

 

 Yes

0.44 (0.38–0.51)

< 0.001

0.60 (0.50–0.73)

< 0.001

 Unknown

0.56 (0.40–0.78)

< 0.001

0.77 (0.54–1.09)

0.145

HR Hazard ratio, CI confidence interval

aOnly patients diagnosed after 2010 were included

We hypothesized that there was interaction between hormonal status (positive vs. negative) and the histology (SCC vs. IDC) in the analysis of OS. We performed a subgroup analysis and noticed that positive (vs. negative) hormonal status was significantly associated with improved OS in IDC (P < 0.01) patients, but not in the SCC (P = 0.042) patients (Fig. 1, Interaction test, P = 0.023). However, endocrine therapy was also associated with improved OS for the HR-positive IDC patients (HR = 0.61, 95%CI 0.48–0.77, P < 0.001), as well as for the HR-positive SCC patients (HR = 0.30, 95%CI 0.15–0.59, P < 0.001) (Fig. 2), after adjusting for age, race, comorbidity score, grade, T-stage, N-stage, M-stage, and chemotherapy.
Fig. 1

Kaplan-Meier survival analysis stratified by HR status in (a) IDC and (b) SCC patients

Fig. 2

Kaplan-Meier survival analysis stratified by endocrine therapy in (a) HR-positive IDC patients, and (b) HR-positive SCC patients

Discussion

Prognosis of SCC patients

Previous studies have shown that SCC of the breast is more likely to be HR-negative and is associated with worse clinical outcomes [2, 8, 9]. Hennessy et al. [2] reported that the 5-year overall survival (OS) rates of 33 and 137 SCC patients selected from the M.D. Anderson Cancer Center and the SEER database, respectively, were 40 and 64%, respectively. In an update, Yadav et al [9] reported a 5-year cancer-specific survival rate of 63.5% for 445 SCC patients who were collected from the SEER database. Due to the rarity of SCC, only the data from the national cancer database is able to provide adequate statistical power to study the prognosis of SCC. However, several important prognostic factors, and the information of adjuvant therapies were lacking in the SEER database. In contrast, the NCDB database provides more prognostic factors (e.g comorbidity score, HER2 status and LVI status), as well as the information of adjuvant therapies (chemotherapy and endocrine therapy), therefore allows a more accurate estimation with less bias. In this study, we observed that the SCC patients had poorer clinicopathological features (e.g., T3–4, grade III, HR-negative disease) than the IDC patients. The adjusted analysis demonstrated that the SCC patients had significantly worse clinical outcomes than the IDC patients in both the 2004–2014 and 2010–2014 (HER2 status adjusted) cohorts. In consistent with previous studies, we confirmed that SCC (vs. IDC) is associated with poorer OS, after adjusting for more prognostic factors and adjuvant therapies.

SCC & systemic therapies

The concept that SCC has worse clinical outcomes than IDC is likely to affect the choice of treatments in the clinical practices. This is confirmed in our study that chemotherapy was more prevalent in low-risk (HR+/HER2-/LN-) SCC (vs. IDC) patients (42.9% vs. 18.7%, P = 0.002). However, whether the SCC is responsive to chemotherapy is still unknown. Hennessy et al. [2] and Zhang et al. [6] reported that they used no responses were observed in their SCC patients after neoadjuvant chemotherapy. Only two case-reports [10, 11] have suggested that cisplatin-based chemotherapy is able to achieve long-term control, but these results need further verification. In our study, we noticed that SCC (vs. IDC) was significantly associated with no responses to neoadjuvant chemotherapy (20% vs. 5.05%, P = 0.019). Therefore, the benefit of chemotherapy in SCC patients remains unknown.

In this study, we observed that the endocrine therapy was less performed in the HR-positive SCC (51.6%) patients, than in the HR-positive IDC (70.5%) patients. A contributing reason could be that endocrine therapy in the head & neck or esophageal SCC patients is not useful in clinical practices [12, 13], even if the in vitro evidences [14, 15] had suggested the role of tamoxifen for SCC of the oral cavity or esophagus. However, SCC of the breast might possibly be different from the head & neck SCC. A recent study used whole-exome sequencing to show that the SCC components have nearly identical landscapes of somatic mutations to their adjacent IDC component, suggesting that SCC may originate from the IDC [3]. Since the role of endocrine therapy had been established in IDC patients, it is possible the endocrine therapy would also be beneficial in SCC patients. In the analysis of prognostic factors of OS, we observed a significant interaction between the HR status and the histology (SCC vs. IDC). The HR status was prognostic only for IDC patients, but not for SCC patients. Despite of this, we still observed that the endocrine therapy significantly improves the OS in HR-positive IDC and SCC patients. Taken together, we suggested that endocrine therapy should remain as the standard treatment for HR-positive SCC patients. Ng et al. [5] studied the landscape of somatic genetic alterations of SCC and reported that TP53(78%) and PI3KCA(44%) are the most frequently mutated genes in SCC. They proposed that the mutation affecting genes might result in the Wnt and mTOR pathway activation. Future studies are warranted to investigate whether relevant pathway inhibitors could be used for SCC patients.

SCC & local therapy

We assessed the influence of the SCC component on the local therapy. SCC patients had a slightly lower rate of BCS, when compared to IDC patients (58.3% vs. 65.4%, P = 0.048). The underlying reason could be that the SCC patients had larger tumor than IDC patients (T3–4: 23.1% vs. 4%). Among patients with BCS, RT was used in 65.3 and 83.0% of the SCC and IDC patients, respectively. Currently, evidence that support the use of RT for SCC is lacking. Hennessy et al. [2] reported that 4 out of 19 SCC patients treated with RT had locoregional relapse within the irradiated field, suggesting that SCC might be radioresistant. Two studies [16, 17] reported no benefit of RT on OS, but the small sample sizes in these studies limited their statistical power. Using the SEER database, Wu et al. [18] reported that RT was significantly associated with improved OS but not cancer-specific survival, which is difficult to explain. Furthermore, they reported that RT was significantly associated with improved CSS in stage II SCC patients, but the analysis was not adjusted for ER, PR or HER2. Thus, the role of RT as an adjuvant local control therapy after surgery remains controversial.

Limitations

First, it is possible that the IDC patients may have a small proportion of SCC component area. Without pathological confirmation, grouping the cases into IDC, and SCC might not be always accurate. However, a detailed histopathology examination is impossible in mining large database, such as NCDB. The large sample size of this study population is able to compensate this limitation. Second, nonrandomized comparisons of treatment effects are prone to providing misleading estimations. One study [19] showed that the treatment effect of RT in breast cancer was over-estimated in observational data compared with randomized clinical trial data. This effect is reasonable as the “treatment-by-indication” bias can never be eliminated in observational data. Therefore, we did not estimate the survival benefit of chemotherapy, as patients with more advanced diseases are prone to receive chemotherapy. However, estimation of the survival benefit of endocrine therapy in HR-positive patients is less likely to be affected by the “treatment-by-indication” bias. HR-positive is the only indication for endocrine therapy. In addition, the decision to implement the endocrine therapy is less likely to be influenced by the comorbidity status. Thus, estimation of the survival benefit of endocrine therapy using observational data is reasonable. Due to the rarity of SCC of the breast, a prospective, randomized study for SCC cannot be realistically implemented. Third, the NCDB did not have information regarding trastuzumab therapy. Whether trastuzumab would be appropriate for HER2-positive SCC patients remains unclear. The lack of information regarding local relapse, metastatic relapse and cancer-specific survival is also one of the limitations. Fourth, there is a growing awareness of an association between SCC of the breast and implants. But the significance of the association is unclear due to the rarity of this situation [20, 21, 22]. The NCDB database does not have the information about the history of breast implants augmentation before the diagnosis of SCC, therefore limits our understanding about this issue.

Conclusions

In this study, we show that compared with IDC, SCC is associated with poorer clinicopathological outcomes. The treatment patterns differ between IDC and SCC. Radiotherapy after BCS is used less often for SCC (vs. IDC) patients. Chemotherapy is used more often for low-risk (HR+/HER2-, node-negative) SCC (vs. IDC) patients. Endocrine therapy is used less often in HR-positive SCC (vs. IDC) patients. In addition, SCC is less likely to response to chemotherapy, and is associated with worse clinical outcomes. Although the HR status is not prognostic in SCC patients, endocrine therapy is still associated with improved OS in HR-positive SCC patients.

Notes

Acknowledgements

The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed or the conclusions drawn from these data by the investigator. We appreciated Qian Ouyang for her assistance in the analysis of the study.

Funding

This study was supported by Guangdong Science and Technology Department (2017B030314026). The role of the funding body was to provide financial support for the cost of language editing service, as well as the publication charges.

Availability of data and materials

The data is available to all readers upon the readers’ request.

Authors’ contributions

LZ: Designed the study, collected and analyzed the data, wrote the manuscript, and approved it for final publication. KC: Designed the study, wrote and revised the manuscript, and approved it for final publication. Both of the authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval and consent to participate

This study was an epidemiological study using de-identified data from the NCDB database. Therefore, consent for patient participation and study publication was not required. The study approval was waived by the ethical committee of Yale University and Sun Yat-sen Memorial Hospital.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary material

12885_2018_5212_MOESM1_ESM.pdf (63 kb)
Additional file 1: Figure S1. Kaplan-Meier survival analysis stratified by histology (IDC vs. SCC) and nodal status in a) HR-positive and b) HR-negative patients. (PDF 62 kb)

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Copyright information

© The Author(s). 2019

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  1. 1.Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationSun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Breast Surgery, Breast Tumor CenterSun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  3. 3.Department of Biostatistics, School of Public HealthYale UniversityNew HavenUSA

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