Breast carcinoma in situ : An observational study of tumor subtype, treatment and outcomes

TLDR: The results demonstrate that BCIS appears to alter the prognosis associated with the TN subtype, and BCS plus R was a preferable option and resulted in survival rates that were better than those achieved with mastectomy; thus, SLNB should be considered as an appropriate assessment of axillary staging in patients with BCIS.

Abstract: // Qi Wu 1 , Juanjuan Li 1 , Si Sun 2 , Shan Zhu 1 , Chuang Chen 1 , Juan Wu 3 , Qian Liu 1 , Wen Wei 1 and Shengrong Sun 1 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 2 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China 3 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China Correspondence to: Shengrong Sun, email: // Keywords : breast carcinoma in situ, tumor subtype, treatment, outcomes Received : September 14, 2016 Accepted : November 23, 2016 Published : December 02, 2016 Abstract Background & Aims: To evaluate the clinical presentation, treatment and outcome of patients with breast carcinoma in situ (BCIS) with special emphasis on the role of the tumor subtype and local treatment in these patients. Methods: Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM). Results: In all, 6867 patients with BCIS were eligible during the 2010-2013 study period. Compared with the hormone receptor (HoR)+/HER- subgroup, patients with triple negative (TN) breast cancer were more likely to have tumors that were higher in grade and larger in size; they were also more likely to have tumors with ductal and comedo histology and were less likely to have tumors with cribriform and papillary histology (each P < 0.05). During the follow-up period, patients with TN breast cancer had an OS of 97.0% compared with 98.6 % in the HoR+/HER- subgroup ( P < 0.05). Furthermore, the BCSM rate was 1.0% for the TN group compared with 0.1% for the HoR+/HER- subgroup ( P < 0.05). Multivariate analysis revealed that patients with TN MBC had a poorer OS and BCSM ( P <0.05). Multivariate analysis of OS with respect to the local treatment history showed that patients who received breast-conserving surgery (BCS) combined with radiotherapy (R) were more likely to have an improved OS ( P < 0.05). Moreover, the results demonstrated that patients who underwent SLNB were more likely to have a lower BCSM ( P < 0.05). Conclusions: The results demonstrate that BCIS appears to alter the prognosis associated with the TN subtype. Meanwhile, BCS plus R was a preferable option and resulted in survival rates that were better than those achieved with mastectomy; thus, SLNB should be considered as an appropriate assessment of axillary staging in patients with BCIS.

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Oncotarget2361
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www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 2), pp: 2361-2371
Breast carcinoma in situ: An observational study of tumor
subtype, treatment and outcomes
Qi Wu
1
, Juanjuan Li
1
, Si Sun
2
, Shan Zhu
1
, Chuang Chen
1
, Juan Wu
3
, Qian Liu
1
, Wen
Wei
1
and Shengrong Sun
1
1
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China
2
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China
3
Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P. R. China
Correspondence to: Shengrong Sun, email: sun137@sina.com
Keywords: breast carcinoma in situ, tumor subtype, treatment, outcomes
Received: September 14, 2016 Accepted: November 23, 2016 Published: December 02, 2016
ABSTRACT
Background & Aims: To evaluate the clinical presentation, treatment and outcome
of patients with breast carcinoma in situ (BCIS) with special emphasis on the role of
the tumor subtype and local treatment in these patients.
Methods: Using data obtained by the Surveillance, Epidemiology, and End Results
(SEER) program from 2010-2013, a retrospective, population-based cohort study was
conducted to investigate tumor subtype-specic differences in various characteristics,
overall survival (OS) and breast cancer-specic mortality (BCSM).
Results: In all, 6867 patients with BCIS were eligible during the 2010-2013 study
period. Compared with the hormone receptor (HoR)+/HER- subgroup, patients with
triple negative (TN) breast cancer were more likely to have tumors that were higher
in grade and larger in size; they were also more likely to have tumors with ductal and
comedo histology and were less likely to have tumors with cribriform and papillary
histology (each P < 0.05). During the follow-up period, patients with TN breast cancer
had an OS of 97.0% compared with 98.6 % in the HoR+/HER- subgroup (P < 0.05).
Furthermore, the BCSM rate was 1.0% for the TN group compared with 0.1% for the
HoR+/HER- subgroup (P < 0.05). Multivariate analysis revealed that patients with TN
MBC had a poorer OS and BCSM (P <0.05). Multivariate analysis of OS with respect
to the local treatment history showed that patients who received breast-conserving
surgery (BCS) combined with radiotherapy (R) were more likely to have an improved
OS (P < 0.05). Moreover, the results demonstrated that patients who underwent SLNB
were more likely to have a lower BCSM (P < 0.05).
Conclusions: The results demonstrate that BCIS appears to alter the prognosis
associated with the TN subtype. Meanwhile, BCS plus R was a preferable option and
resulted in survival rates that were better than those achieved with mastectomy;
thus, SLNB should be considered as an appropriate assessment of axillary staging in
patients with BCIS.
INTRODUCTION
The term breast carcinoma in situ (BCIS)
encompasses lesions that contain abnormal epithelial cells
that are completely conned within breast lobules and/or
ducts without invasion beyond the basement membrane.
BCIS includes a variety of pathological types. The 2 major
types of breast carcinoma in situ are ductal carcinoma in
situ (DCIS) and lobular carcinoma in situ (LCIS). The
incidence of BCIS increased rapidly after the introduction
of mammography as a population screening tool and has
subsequently increased at a slower rate [1-4].
In the majority of patients, BCIS is primarily viewed
as an indicator of an increased risk for invasive breast
cancer. Moreover, several studies have revealed that BCIS
lesions tend to be small in size, grade II or III, and widely
positive for estrogen receptor (ER) and progesterone
receptor (PR), but HER2 testing is not a routine part of
the pathologic evaluation [5, 6]. However, studies have
also suggested that high nuclear grade DCIS lesions are
Research Paper

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often negative for ER and that they overexpress HER2.
Furthermore, this subtype may be associated with reduced
survival, and thus targeting HER2 is a potential treatment
strategy for HER2-overexpressing DCIS. Additionally,
a new Van Nuys Prognostic Index (VNPI) is used as an
independent predictor of local recurrence; this new index
has a new formula that accounts for tumor size, margin
width, pathologic classication, and age [7].
Traditional treatment has been mastectomy, whereas
breast-conserving surgery (BCS) is a feasible surgical
option for select patients. In addition to BCS, the effect
of sentinel lymph node biopsy (SLNB) in BCIS remains
unclear. Based on the current standards, SLNB has been
recommended as a less invasive method compared with
axillary lymph node dissection (ALND) for the staging
of patients with early invasive ductal carcinoma. We
speculate that SLNB might be approved as an effective
method to detect axillary lymph nodes (ALNs) in patients
with BCIS. The benet of radiotherapy in terms of a
signicantly reduced risk of local recurrence (LR) in those
who receive BCS has been demonstrated by several large
randomized controlled trials [8, 9]. However, the idea that
radiotherapy should be avoided in selected low-risk cases
remains uncertain.
The clinical characteristics of BCIS and the optimal
approaches to treatment are topics of uncertainty and
concern for both patients and clinicians. Therefore, this
article will evaluate the clinical presentation, treatment
and outcomes of patients with BCIS, with special stress
on the role of breast cancer subtype, BCS and SLNB.
RESULTS
Clinical and tumor characteristics
In all, 6867 patients with BCIS were eligible
during the 2010-2013 study period. We excluded
54,190 patients whose medical records did not contain
information on breast cancer subtype and 241 patients
whose survival times were classied as unknown in the
analysis. Information was available for 4324 patients with
BCIS in the HoR+/HER- subgroup, 1409 patients in the
HoR+/HER+ subgroup, 795 patients in the HoR-/HER+
subgroup and 429 patients in the triple-negative (TN)
subgroup, who were all included in this study.
Differences in patient demographics, cancer
characteristics, treatments, and outcomes among the
subgroups are summarized in Table 1. Compared with the
HoR+/HER- subgroup, patients with TN breast cancer
were more likely to have tumors that were higher in grade
and larger and were more likely to have tumors with ductal
and comedo histology; these patients were less likely to
have tumors with cribriform and papillary histology (each
Figure 1: Weighted Kaplan-Meier curves of overall survival(OS) and breast-cancer-specic mortality(BCSM). A. OS
is based on tumor subtype. B. OS is based on HER2 status. C. OS is based on tumor size. D. BCSM is based on tumor subtype. E. BCSM
is based on HER2 status.

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Table 1: Patient characteristics within subgroups

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P < 0.05). Patients within the HoR-/HER+ subgroup had
tumors that were, in general, higher in grade and larger
in size compared with tumors of patients in the HoR+/
HER- subgroup. Furthermore, patients in the HoR-/
HER+ subgroup were the most likely to have tumors with
comedo and papillary histology. With respect to treatment
options, patients within the four subgroups tended to
receive breast-conserving surgery (BCS) and sentinel
lymph node biopsy (SLNB).
Survival analysis
A weighted Kaplan-Meier analysis was used to
determine overall survival (OS) and breast cancer-specic
mortality (BCSM), which were based on breast cancer
subtype and HER2 status, of the patients in the subgroups.
Survival curves for the subgroups were generated (Figure
1). At the median follow-up of 22 months, patients with
TN breast cancer had an OS of 97.0% compared with
* P values calculated by Pearson Chi squared testing; Bold if statistically signicant, P< 0.05
y: years, mm: millimeter, y: years, BCS: breast-conserving surgery, HoR: hormone receptor, TN: triple negative, LN: lymph
node, SLNB: sentinel lymph node biopsy, ALND: axillary lymph node dissection.

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Table 2: Cox proportional hazards regression model analysis of overall survival (OS) and breast
cancer-specic mortality (BCSM)