The receptor expression pattern in ductal carcinoma in situ predicts recurrence

doi:10.1016/j.amjsurg.2006.04.002

The American Journal of Surgery

Volume 192, Issue 1, July 2006, Pages 68-71

https://doi.org/10.1016/j.amjsurg.2006.04.002 Get rights and content

Abstract

Background

The treatment of ductal carcinoma in situ (DCIS) is based on size and pathologic morphology. We hypothesized that as with invasive breast cancer, receptor expression in DCIS is important for predicting recurrence.

Methods

Retrospective review from 1990 through 2002 identified 94 DCIS patients who had documented estrogen receptor (ER), progesterone receptor (PR), p53, Her-2/neu (HER), tumor characteristics, type of surgery, use of radiation or tamoxifen, and site of recurrence.

Results

Median age and tumor size was 57.5 years and 2.0 cm, respectively. Median follow-up was 4 years. Overall recurrence rate was 6%. The ER-positive/PR-negative/HER-positive receptor pattern represented 50% (3 of 6) of total recurrences (P = .01). The length of disease-free-survival in the ER-positive/PR-negative/HER-positive receptor pattern was significantly shorter than in the rest of the patients (P = .0011).

Comments

Receptor expression may be important in DCIS for predicting recurrence. HER positivity, even with ER positivity, is significantly associated with a higher risk of recurrence.

Section snippets

Study design and patients

An Institutional Review Board–approved retrospective study was conducted of all patients diagnosed with DCIS between 1990 and 2002 at the University of Arkansas for Medical Sciences. Only patients who had complete evaluation of ER, PR, HER, and p53 were included in the study. Immunohistochemistry was used to identify ER, PR, HER, and p53 receptor status.

Data collection

Data collected included demographics, pathology results, treatment, and disease status at last follow-up. The patient’s medical record, the

Study patients

One hundred sixty-nine patients with a diagnosis of DCIS were identified. Thirty-seven patients were excluded because of microinvasive disease. Of the remaining 132 patients, 38 were excluded based on lack of available tissue to perform immunohistochemistry for receptors. Thus, 94 patients were available for data analysis. The median age of the patients was 57.5 years (25th to 75th percentile range = 48 to 66). The median follow-up time was 4 years (25th to 75th percentile range = 2 to 7).

Pathology

The

Comments

DCIS is a unique biologic and clinical entity by virtue of its significant dissimilarities to other epithelial in situ lesions. For example, in situ carcinoma of the esophagus or rectum can be excised with the intent to cure without adjuvant treatment. On the contrary, DCIS always poses a dilemma regarding the optimal therapeutic management because of the possibility to progress or recur as a potentially life-threatening invasive cancer. That is, half of recurrences in those initially

Acknowledgments

Supported by the Susan G. Komen Breast Cancer Clinical Fellowship (J. K. and R. L.) and the Virginia Clinton Kelley/Fashion Footwear Association of New York Breast Cancer Research Fellowship (J. K. and R. L.).

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Cited by (38)

Ductal Carcinoma in Situ Biomarkers in a Precision Medicine Era: Current and Future Molecular-Based Testing
2019, American Journal of Pathology
Citation Excerpt :
The role of routine testing for human epidermal factor 2 (HER2) in DCIS remains unclear. Although HER2 expression in DCIS is correlated with high nuclear grade and increased risk of recurrence and negatively correlated with ER and PR expression,51–54 it is not currently recommended to routinely test DCIS for HER2. The effect of radiotherapy with or without trastuzumab in HER2-positive patients with DCIS who have had a lumpectomy is being evaluated in the National Surgical Adjuvant Breast and Bowel Project B43 study, which is expected to be completed in 2019 (Clinical Trial Identifier: NCT00769379).
Historically, ductal carcinoma in situ (DCIS) of the breast has been managed aggressively with surgery and radiotherapy because of a risk of progression to invasive ductal carcinoma. However, this treatment paradigm has been challenged by overtreatment concerns and evidence that suggests that DCIS can be stratified according to risk of recurrence or risk of progression to invasive disease. Traditional methods of risk stratification include histologic grade and hormone receptor status. Recent technological advancements have enabled an era of precision medicine, where DCIS can be molecularly analyzed by tools, such as next-generation DNA and RNA sequencing, to identify molecular biomarkers for risk stratification. These findings have led to the development of tools such as the Oncotype DX Breast DCIS Score, a gene expression–based assay with the potential to prevent overtreatment in low-risk disease.
Ductal carcinoma in situ and intraoperative partial breast irradiation: Who are the best candidates? Long-term outcome of a single institution series
2019, Radiotherapy and Oncology
Citation Excerpt :
The potential role of biological markers in predicting disease outcome in DCIS has not been investigated as extensively as for invasive cancer and is challenged by conflicting results. A number of studies, including a meta-analysis [32–34], found that ER/PgR negativity and HER2 positivity were independent predictors of recurrence, often associated with each other [34], so that the corresponding phenotype was correlated with increased risk of recurrence, which is in line with our results [35]. In particular, HER2 overexpression appeared to be associated with increased cell proliferation, higher cell motility and larger lesion extent with a greater probability of occult DCIS foci in the breast [36].
To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT).
From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1–2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable).
Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001).
When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups.
The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice.
Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ
2017, Human Pathology
Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n = 43) and pure DCIS (n = 82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, “tumor thickness,” extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor “thickness” was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.
Expression of HER2neu in Ductal Carcinoma in situ is Associated with Local Recurrence
2012, Clinical Oncology
Citation Excerpt :
These subtypes were defined using specimens of invasive cancers, but these subtypes are also evaluable in DCIS. The utility of this classification scheme to improve our ability to predict clinical outcomes in DCIS has not been widely studied [13–19]. The objectives of this study were to estimate the relative frequencies of the different intrinsic molecular subtypes in DCIS (defined by ER, PR and HER2neu staining) and to determine if these subtypes are associated with the development of local recurrence in women with DCIS treated by breast-conserving therapy.
Determination of the risk of recurrence after local excision of ductal carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on immunohistochemical staining to oestrogen receptor (ER), progesterone receptor (PR) and HER2neu improved risk prediction in invasive breast cancer, but few studies have evaluated if molecular classification of DCIS predicts local recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to determine if molecular classification predicts local recurrence after breast-conserving therapy for DCIS.
We reviewed the records of patients with DCIS treated between 1987 and 2000, carried out a pathology review and immunohistochemical staining for ER, PR and HER2neu and categorised cases into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu–), luminal B (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER–, PR–, HER2neu+), triple negative (ER–, PR–, HER2neu–)]. We evaluated the association between the molecular subtype and the development of local recurrence.
In total, 180 cases of DCIS were included in the study (luminal A, n = 113; luminal B, n = 25; HER2neu type, n = 29; triple negative, n = 13). The median follow-up time was 8.7 years. We observed higher rates of local recurrence among luminal B (40%) and HER2neu type (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On multivariable analysis, HER2neu overexpression was associated with an increased risk of local recurrence (hazard ratio = 1.98; 95% confidence interval: 1.11, 3.53, P = 0.02).
HER2neu expression in DCIS is a significant predictor of local recurrence, whereas luminal A and triple negative phenotypes are associated with relatively low risks of local recurrence.
Improved outcomes of breast-conserving therapy for patients with ductal carcinoma in situ
2012, International Journal of Radiation Oncology Biology Physics
Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2⁺ DCIS.
We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40–52 Gy) and 99% (244) received a tumor bed boost (8–18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003.
With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR⁺HER-2⁻, 27 were ER/PR⁺HER-2⁺, 6 were ER⁻/PR⁻HER-2⁺, and 6 were ER⁻/PR⁻HER-2⁻. On univariable analysis, HER-2⁺was significantly associated with Grade III, ER⁻/PR⁻, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2⁺.
In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated with HER-2⁺DCIS included more extensive DCIS, Grade III, ER⁻/PR⁻, central necrosis, comedo subtype, and postmenopausal status. Further follow-up and additional studies are required to confirm these results.
Aromatase and in situ estrogen production in DCIS (ductal carcinoma in situ) of human breast
2010, Journal of Steroid Biochemistry and Molecular Biology
Ductal carcinoma in situ or DCIS belongs to intraductal proliferative lesions, which are a group of cytologically and architecturally diverse ductal proliferations, typically originating from the terminal duct–lobular units. In these intraductal proliferative diseases, estrogens are considered to be involved in the progression of the disease especially from ductal non-neoplastic hyperplasia to DCIS and possibly development of invasive carcinoma from DCIS. Estrogen receptor (ER) alpha is abundantly expressed in atypical ductal hyperplasia and low grade DCIS. Suppression of estrogenic actions using tamoxifen resulted in inhibition of recurrence of DCIS and/or of progression into invasive carcinoma. Intratumoral estrogen concentration in DCIS determined by liquid chromatography/electrospray tandem mass spectrometry is significantly higher than that in non-neoplastic breast tissues with statistically not lower than that in invasive carcinoma. Aromatase mRNA expression in both stromal and parenchymal cells of DCIS determined by quantitative RT-PCR following laser capture microdissection was also much higher than that in non-neoplastic breast, although lower than that in invasive carcinoma. Immunohistochemistry of aromatase also revealed the similar patterns of immunolocalization as in invasive carcinoma. Aromatase is overexpressed in noninvasive breast malignancies including DCIS and results in elevated concentrations of intratumoral estradiol. These findings could provide the scientific rationale as to employing aromatase inhibitors in the management of ER positive DCIS patients.

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Clinical surgery–AmericanThe receptor expression pattern in ductal carcinoma in situ predicts recurrence

Abstract

Background

Methods

Results

Comments

Section snippets

Study design and patients

Data collection

Study patients

Pathology

Comments

Acknowledgments

Surg Clin N Am

Eur J Cancer

Surg Clin North Am

Exp Mol Pathol

Adv Cancer Res

Breast

Needle localization of nonpalpable breast masses

Arch Surg

Nonpalpable breast lesionsDiagnosis with slightly overpenetrated screen-film mammography and hook wire-directed biopsy in 1,014 cases

Radiology

Mammary duct proliferation in the elderly

Cancer

Breast cancer and atypia among young and middle-aged womenA study of 110 medicolegal autopsies

Br J Cancer

Continued local recurrence of carcinoma 15-25 years after a diagnosis of low-grade ductal carcinoma in situ of the breast treated only by biopsy

Cancer

Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone

JAMA

Clinical surgery–American
The receptor expression pattern in ductal carcinoma in situ predicts recurrence