Differences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case–Control Study (KROG 13-06)

doi:10.1016/j.clbc.2015.01.008

Clinical Breast Cancer

Volume 15, Issue 5, October 2015, Pages 353-361.e2

https://doi.org/10.1016/j.clbc.2015.01.008 Get rights and content

Abstract

Purpose

We designed the present study to investigate differences in prognostic factors and failure patterns between patients with invasive micropapillary carcinoma or carcinoma with micropapillary component (IMPC) and randomly matched patients with invasive ductal carcinoma (IDC) of the breast at multiple institutions of the Korean Radiation Oncology Group (KROG).

Materials and Methods

This retrospective multicenter study was performed using subjects treated from January 1999 to November 2011. Female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy were considered for this study. Exact matches were made for age (± 3 years), pathologic tumor and node stage, treatment method (surgery with or without radiotherapy), and period when surgery was performed (within 1 year) at the same institution.

Results

A total of 534 patients were analyzed. The median follow-up period was 59 months in both groups. In the comparison of clinicopathologic characteristics, rates of lymphovascular invasion (LVI) and nuclear grade III were both significantly higher in IMPC than in IDC (P < .001, P = .01, respectively). During the follow-up period, recurrences developed in 40 patients with IMPC (15.0%) and 21 with IDC (7.9%). Locoregional recurrence (LRR) developed in 22 patients with IMPC (8.2%) and 10 with IDC (3.7%). The rate of distant metastasis did not differ between the 2 groups (P = .52). LRR-free survival (P = .03) and recurrence-free survival (P = .007) were significantly different between the 2 groups, but overall survival was not (P = .67).

Conclusion

IMPC is associated with a higher rate of LVI, high nuclear grade, and a propensity for LRR compared to IDC. Modification of the locoregional treatment modality might be needed in this pathologic subtype of breast cancer.

Introduction

Invasive micropapillary carcinoma (IMPC) is a relatively rare variant of invasive breast cancer, accounting for approximately 3% to 8% of all breast cancer cases.1, 2, 3 The hallmark of IMPC is the presence of small tumor cell nests, which appear as micropapillae surrounded by clear stromal spaces.4, 5 Pathologically, it is known for its high proclivity for lymphovascular invasion (LVI), lymph node (LN) metastasis, and poor prognosis.6, 7, 8

Despite the strong possibility of an unfavorable outcome, the low incidence of IMPC has made it difficult to develop a standard treatment, and treatment of IMPC remains the same as that for invasive ductal carcinoma (IDC). However, the characteristics that distinguish IMPC from IDC should be considered in order to properly manage treatment and improve ultimate outcomes.

We previously reported outcomes based on differences between IMPC and IDC; IMPC showed different clinical characteristics that were known to be poor prognostic factors, such as a higher rate of nuclear grade, LVI, and extracapsular extension (ECE), and had dismal outcomes with a higher rate of locoregional recurrence (LRR) compared to stage-matched IDC.⁹ However, that retrospective study was conducted at a single institution, suggesting an inherent selection bias. Furthermore, the sample size was too small to derive concrete conclusions.

To address these shortcomings, our current study was planned with an independently collected group of patients from the Korean Radiation Oncology Group (KROG) as study subjects. We analyzed differences in prognostic factors and failure patterns between IMPC and IDC patients of a similar age, with the same stage of disease, and identical treatment at the same hospital. We expected that our findings would suggest optimal modifications that could be made to the standard management of IDC in order to improve treatment outcomes of IMPC.

Section snippets

Patients

This multicenter retrospective study was conducted with breast cancer patients who received treatment at 7 Korean institutions of the KROG between January 1999 and November 2011. This study was approved and exempted from patient permission by all institutional review boards.

Women with breast cancer who had IMPC pathology and who received standard treatment for breast cancer were considered for this study, regardless of the extent of the disease or the type of surgery performed. Any patient who

Patients

A total of 315 women with IMPC who received curative standard treatment without neoadjuvant chemotherapy were identified at 7 institutions. The diagnostic criterion of IMPC was slightly different according to the institution, but in general was more than 90% of the tumor showing a micropapillary pattern. Among these IMPC cases, 48 could not be matched with IDC and 8 experienced recurrence, with 5 of these being LRR. A total of 534 patients (267 IMPC and 267 matched IDC) were finally enrolled

Discussion

We previously reported a retrospective single-institution study of IMPC of the breast and concluded that IMPC had a higher rate of poor prognostic factors and LRR than IDC.⁹ On the basis of that study, we suggested postoperative RT field modification in IMPC. However, the limitations of this retrospective single-institution study with a small sample size made it hard to adapt the results to routine clinical practice.

The present multi-institutional stratified random matching study was conducted

Disclosure

The authors have stated that they have no conflicts of interest.

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Cited by (39)

Radiological characteristics of invasive micropapillary carcinoma of the breast
2024, Clinical Radiology
To analyse the various imaging features of invasive micropapillary carcinoma (IMPC), a distinct variant of breast cancer, by mammography, ultrasound, and contrast-enhanced mammography.
This study included 68 female patients with histopathologically proven invasive micropapillary carcinoma who underwent mammography, ultrasound, and contrast-enhanced mammography examinations. The findings encountered by each imaging tool were analysed using the Breast Imaging Reporting and Data System (BI-RADS) lexicon.
In this retrospective study, 64.7% of cases were of the pure form of IMPC. Most of the cases showed an aggressive clinical course, with lymphovascular invasion noted in 76.5% of cases, while 60.3% of cases showed associated pathological lymphadenopathy. The N3 stage was reported in 25% of cases. On analysing the mammographic and ultrasound imaging findings, a significant association between irregular shape and a non-circumscribed margin with IMPC was found. Associated calcification was noted in 47% of cases. Pathological enhancement of moderate or marked conspicuity was noted in cases that underwent contrast-enhanced mammography, with the most commonly encountered finding being enhancing irregular and non-circumscribed masses.
The mammographic and ultrasound imaging features of IMPC are indistinguishable from other aggressive types of breast cancer. At contrast-enhanced mammography examination, pathological enhancement of moderate to marked conspicuity was shown in all cases. The observed strong association of IMPC with lymphovascular invasion and lymph node metastasis with higher nodal stage in this study mandate meticulous sonographic examination of the axilla, as well as the infra, and supraclavicular regions if pathological axillary lymphadenopathy was noted.
Nomograms for predicting overall survival and cancer-specific survival in patients with invasive micropapillary carcinoma: Based on the SEER database
2023, Asian Journal of Surgery
Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer that lacks a prognostic prediction model. Its treatment and prognostic factors remain controversial. Our study aimed to develop nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in IMPC patients.
A total of 2149 patients confirmed to have IMPC between 2003 and 2018 were selected from the Surveillance, Epidemiology and End Results (SEER) database. They were divided into training and validation cohorts. Univariate and multivariate Cox regression analyses were used to identify significant independent prognostic factors. The nomograms were used to predict 3- and 5-year OS and CSS. The training and validation cohorts were used to verify the nomograms internally and externally. The predictive capability of the nomograms was evaluated by the consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve.
In the study, 2149 IMPC patients were randomized to a training group (n = 1611) and a validation group (n = 538). Age, T stage, N stage, ER, radiotherapy, and surgery were identified as independent prognostic factors for OS and CSS. These variables were selected to construct nomograms for IMPC. The C-index (0.768 for OS and 0.811 for CSS) and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomograms. Additionally, DCA showed that the nomograms had higher clinical value than traditional TNM tumor staging.
The models can accurately predict the prognosis of IMPC patients and can aid in providing individualized treatment for patients.
Invasive micropapillary carcinoma of the breast. Long term outcome
2023, Revista de Senologia y Patologia Mamaria
el carcinoma micropapilar infiltrante (CMI) es una variante histológica inusual y potencialmente agresiva caracterizada por primera vez en 1993 por Siriangkul et al. y que no formó parte de la clasificación de la Organización Mundial de la Salud (OMS) hasta 2003, como tumor mamario epitelial. Representa menos del 2% del total de carcinomas invasivos de la mama y se presupone que presenta un pronóstico desfavorable en comparación con otros carcinomas convencionales debido a su elevado tropismo vascular y linfático.
hasta la fecha no existe ningún estudio con un número elevado de pacientes procedentes de un único centro (> 100 casos) con un periodo de seguimiento largo (> 20 años) que compare la supervivencia del CMI con otros carcinomas convencionales no micropapilares. Se ha llevado a cabo un estudio retrospectivo, observacional con un total de 401 pacientes: 174 con CMI y 227 con otros carcinomas convencionales.
el CMI presenta mayor grado histológico, mayor afectación ganglionar y mayor riesgo de metástasis a distancia en comparación con otros carcinomas convencionales de características similares. Sin embargo, en el análisis multivariante considerando factores pronósticos como edad, tamaño tumoral, afectación ganglionar y grado histológico, no se observan diferencias estadísticamente significativas para la supervivencia global y libre de enfermedad entre los CMI diagnosticados en el mismo periodo de tiempo que los casos pareados del grupo control y otros carcinomas convencionales.
la supervivencia global y libre de enfermedad es similar entre el CMI y otros carcinomas convencionales a igual edad, tamaño tumoral, grado histológico y afectación ganglionar.
Invasive Micropapillary Carcinoma of the breast (IMPC) is an unusual and aggressive histological variant characterized for the first time in 1993 by Siriangkul et al. and classified by the World Health Organization in 2003 as an epithelial breast tumor. It represents less than 2% of all invasive carcinomas of the breast and is presumed to have an unfavorable prognosis compared to other conventional carcinomas due to its high vascular and lymphatic tropism.
Until now, there is no study with a large number of patients from a single center with a long follow-up period that compares the survival of IMPC with other conventional non-micropapillary carcinomas. A retrospective, observational study has been carried out with a total of 401 patients: 174 with IMPC and 227 with other conventional carcinomas.
IMPC has a higher histological grade, greater lymph node involvement and a higher risk of distant metastasis compared to other conventional carcinomas. However, in the multivariate analysis considering date of diagnosis, age, tumor size, lymph node involvement and histological grade as variables, no statistically significant differences were observed for overall and disease- free survival between IMPC and other conventional carcinomas.
Overall and disease-free survival is similar between IMPC and other conventional carcinomas considering same age, tumor size, histological grade, and lymph node involvement.
Treatment of pediatric bilateral condylar fractures: A comprehensive analysis
2023, Journal of Stomatology, Oral and Maxillofacial Surgery
Citation Excerpt :
Specifically, fractures on one side were addressed with ORIF whereas those of the contralateral side were managed with IMF, probably to support in correcting the complications associated to occlusion and deviation. A number of studies have investigated different aspects of the condyle mandibular fractures, such as their etiology [53–58], radiographic evaluation [65–68], options for management of BCF [6,11,13,37,51,52], comparison of various treatment techniques [15,21,26,59–61] and follow up of the patients treated for condylar fractures [4,5,9,10,38,39,62–64]. However, there are few studies examining the most appropriate treatment options for the BCF, particularly in pediatric patients [69].
Pediatric bilateral condylar fractures (PBCF) is a rare clinical pathology, where the management is carried out with both conservative and surgical approaches. The purpose of this study was to analyze and compare these two treatment approaches and their associated long term complications in PBCF. An extensive literature review- through the search of online databases- was conducted to survey, collect, analyze and compare the reported outcomes of different treatment modalities for PBCF. The number of studies presenting PBCF case reports was 16, while the number of such retrospective studies included here was 19. Analyses of these studies revealed that the conservative treatment is preferred in PBCF patients younger than 12 years of age. Moreover, a composite approach where the open reduction and internal fixation (ORIF) is carried out for one side while the intermaxillary fixation (IMF) for the contralateral side is frequently reported for the management of PBCF cases; this approach appears effective in improving daily functioning of temporomandibular joint and reducing long term complications. Performing ORIF for one side while IMF for the contralateral side seems the most common treatment approach in PBCF. This study may help in rapid decision making for treatment selection of PBCF patients while minimizing the risk for late complications.
The presence of retraction clefts correlates with lymphovascular invasion and lymph node metastasis and predicts poor outcome: Analysis of 2497 breast cancer patients
2022, Annals of Diagnostic Pathology
Citation Excerpt :
The cells exhibit reversed polarity with the glandular epithelial cells located on the outer surface of the cell nests, revealed by immunohistochemical stain for epithelial membrane antigen (EMA). IMPC is associated with higher incidence of lymphovascular invasion (LVI), lymph node metastasis and poor prognosis [4,5]. Some invasive breast cancers have tumor cell clusters surrounded by clear stromal space similar to IMPC, but lack the morphological and immunohistochemical characteristics of IMPC.
Some invasive breast carcinomas are surrounded by a clear space that separate the tumor cells from the adjacent stroma, similar to invasive micropapillary carcinoma (IMPC), but lack the thin strands of connective tissue that separate the cells and characteristic “inside-out” growth pattern of IMPC on immunohistochemical stain for EMA. We consider the presence of the retraction clefts a common phenomenon that may present as a precursor stage of IMPC (PSIMPC). In this study, a total of 2497 cases of invasive breast carcinomas were prospectively collected. Among 2497 cases of breast cancer, 949 (38.0 %) cases were PSIMPC, 200 (8.0 %) cases were IMPC and 1348 (54.0 %) cases were IBC-NST. LVI was seen in128 of 200 (64 %) IMPC and 364 of 948 (38.0 %) PSIMPC, in contrast to 246 of 1341 (18 %) IBC-NST (P < 0.001). Lymph node metastasis was seen in 147 of 200 (73.4 %) IMPC and 551 of 949 (58 %) PSIMPC, in contrast to 563 of 1345 (42 %) IBC-NST (P < 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) of PSIMPC were 76.8 % and 87.6 %, compared to 63.2 % and 85.9 % in IMPC, 86.2 % and 93.7 % in IBC-NST. PSIMPC demonstrated a more favorable DFS and OS compared to IMPC, but worse DFS and OS compared to IBC-NST. Cox and logistic regression analysis showed that PSIMPC was an independent predictor of DFS and OS. Our findings suggest that the presence of retraction clefts is a precursor state of IMPC, exhibiting IMPC-like features, such as higher incidence of lymphovascular invasion, lymph node metastasis and more aggressive clinical behavior.
Special Histologic Type and Rare Breast Tumors – Diagnostic Review and Clinico-Pathological Implications
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Original StudyDifferences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case–Control Study (KROG 13-06)

Abstract

Purpose

Materials and Methods

Results

Conclusion

Introduction

Section snippets

Patients

Patients

Discussion

Disclosure

Clin Breast Cancer

Pathol Res Pract

Hum Pathol

Hum Pathol

Breast

Pathol Res Pract

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Semin Radiat Oncol

Ann Oncol

The presence of micropapillary features and retraction artifact in core needle biopsy material predicts lymph node metastasis in breast carcinoma

Am J Surg Pathol

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast

Br J Cancer

Original Study
Differences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case–Control Study (KROG 13-06)