|Year : 2016 | Volume
| Issue : 2 | Page : 995-998
Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ
Rafael A. M. Hassan, Jonathan Y Maesaka, Marcos D Ricci, José M Soares, Maíra Teixeira Dória, Edmund C Baracat, José R Filassi
Department of Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil
|Date of Web Publication||25-Jul-2016|
Maíra Teixeira Dória
Department of Obstetrics and Gynecology, University of Sao Paulo, Av. Dr. Eneas Carvalho de Aguiar, 255-10° Andar ICHC, 05403-000, São Paulo
Source of Support: None, Conflict of Interest: None
Context: Surgery is the main form of treatment for ductal carcinoma in situ (DCIS) of the breast. Among other factors, treatment success requires that the surgical margins are free of disease, to reduce the risk of recurrence.
Aims: The purpose of this study was to analyze factors that might be associated with positive margins in patients diagnosed with DCIS.
Settings and Design: A retrospective analysis was performed of hospital databases from the year 2006 to 2014, to identify patients with an initial diagnosis of DCIS made by percutaneous biopsy.
Subjects and Methods: Age, the presence of disease symptoms, lesion size on mammogram, and the presence of estrogen receptors, and their relationship to the surgical margins were evaluated in 249 patients.
Statistical Analysis Used: Shapiro and Wilcoxon–Mann–Whitney tests were used to verify that the data were normally distributed. Chi-squared test was used to verify the independence of the variables.
Results: Lesions measuring 1.55 cm or greater had a relative risk of positive margins after conservative surgery of 1.39 (95% confidence interval [95% CI]: 1.02–1.90). The presence of symptoms had a relative risk of positive margins after conservative surgery of 1.54 (95% CI: 1.17–2.02).
Conclusion: Lesions measuring 1.55 cm or greater and the presence of symptoms are risk factors for positive margins in the treatment of ductal carcinoma in situ. Therefore, these patients need a better surgical planning in order to reduce the risk of positive margins. There is a clear need for large prospective studies to validate our findings and define other factors that might contribute to the success of surgical resection for ductal carcinoma in situ.
Keywords: Breast surgery, ductal carcinoma in situ, surgical margins
|How to cite this article:|
Hassan RA, Maesaka JY, Ricci MD, Soares JM, Dória MT, Baracat EC, Filassi JR. Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ. J Can Res Ther 2016;12:995-8
|How to cite this URL:|
Hassan RA, Maesaka JY, Ricci MD, Soares JM, Dória MT, Baracat EC, Filassi JR. Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ. J Can Res Ther [serial online] 2016 [cited 2020 Sep 30];12:995-8. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/995/172135
| > Introduction|| |
With the development of screening programs for breast cancer, there has been an increase in the diagnosis of ductal carcinoma in situ (DCIS).,,, Surgery is fundamental to the successful treatment of DCIS, and surgical margins are of the utmost importance because they directly affect the risk of disease recurrence.,,, Obtaining resections with safe surgical margins in the case of DCIS continues to be a challenge.,, Therefore, the purpose of this study was to analyze factors that might be associated with positive margins in patients who received a diagnosis of DCIS by percutaneous biopsy.
| > Subjects and Methods|| |
This study involved a retrospective examination of the databases of the institution for the years from 2006 to 2014. Local Ethics Committee approved the study (protocol nos. 100/14 and 497/14, respectively). The inclusion criterion was an initial diagnosis of DCIS obtained by percutaneous biopsy, performed during screening, or an investigation of clinical findings. Patients were excluded from the study if they did not receive surgical treatment or if a review of the percutaneous biopsy material revealed invasive carcinoma.
The initial study population consisted of 258 women. Nine patients were excluded because they had been diagnosed with invasive carcinoma after review of the percutaneous biopsy material (six patients) or did not undergo surgical treatment (three patients). Therefore, 249 patients were included in the final analysis, with 125 patients undergoing mastectomy and 124 patients undergoing conservative surgery [Figure 1]. Patient information, including age and body mass index (BMI), was recorded, as well as mammographic size, the presence of symptoms, nuclear grade, and the presence of estrogen receptors (ERs).
In the conservative surgeries, lesions were identified through a radiopharmaceutical agent, metal guidewire, or palpable change. Lesions were divided into groups of lesions with positive margins and lesions with clear margins. In all cases, mammograms were obtained with digital Hologic Lorad Seleniamammography devices. Margins of the surgical samples were identified with surgical thread by the breast surgeon.
Positive margins were detected by examination of paraffin or frozen sections. According to the protocol of the Departments of Pathology, each specimen was weighed, measured in three dimensions, and painted around the edges to identify the margins. After fixation, the specimens were cut perpendicularly at intervals of 3–5 mm. For the frozen section evaluation, analysis was carried out by using slices of the margin perpendicular to the lesion or by scrape cytology of the margin. According to the protocol of the Instituto do Cancer do Estado de São Paulo, the margins were considered positive when they within 2 mm of the in situ neoplasm. Immunohistochemistry using the streptavidin biotin peroxidase technique was used to analyze expression of ER in resected tumor tissues and percutaneous biopsy samples. Levels of ER were considered positive if more than 1% of the neoplastic cells present exhibited staining in the membrane.
The Shapiro and Wilcoxon–Mann–Whitney tests were used to verify that the data were normally distributed. The univariate analysis involved binary logistic regression for the presence or absence of positive margins correlated with age, BMI, symptom presence, the presence of ERs, and lesion size on the mammogram. The Chi-squared test was used to verify the independence of the variables, which were considered significant when the P < 0.05. The 95% confidence intervals (95% CIs) were calculated for all statistical tests. To find the ideal lesion size on the mammogram that was associated with positive margins, the receiver operator characteristic curve was applied. RStudio Desktop software (version v0.98.953, Foundation for Open Access Statistics, Boston, MA, USA) was used for the analysis.
| > Results|| |
The status of the surgical margins was documented in all 249 patients included in the study. Conservative surgery was performed in 124 cases (49.8%) and mastectomy in 125 cases (50.2%). Positive margins were identified in 104 cases (41.8%), with positive rates of 25% after mastectomy and 59% after conservative surgery. The relative risk of a positive margin after conservative surgery was 2.37 (95% CI: 1.69–3.33).
[Table 1] and [Table 2] report the patients' clinical data. Age and BMI had no association with positive margins after conservative surgery. However, patients with symptoms of DCIS (palpable changes, papillary discharge, or papillary lesion) had a relative risk of positive margins after conservative surgery of 1.54 (95% CI: 1.17–2.02; P = 0.03) and a relative risk of mastectomy of 1.56 (95% CI: 1.23–1.98).
|Table 1: Predictive factors for positive surgical margins in patients receiving conservative surgery|
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|Table 2: Relationship between the predictive factors and the risk of mastectomy|
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All patients in the study underwent mammography before their surgery. The average lesion size on the mammograms was 3.63 cm. In 21 cases, the lesion could not be observed or measured by mammography. In these cases, the diagnosis was made by the breast surgeon based on clinical evaluation, magnetic resonance, and/or ultrasound of the breasts. Lesions with a size of 1.55 cm or greater had a relative risk of positive margins after conservative surgery of 1.39 (95% CI: 1.02–1.90) and a relative risk of mastectomy of 2.14 (95% CI: 1.52–3.03).
Because this study involved a retrospective cohort, anatomopathological data were analyzed on the basis of the presurgical biopsies, with the outcome being the margin status. There was no statistical association of nuclear grade or presence of ERs with positive surgical margins. However, ER negative and an age under 60 years were risk factors for mastectomy [Table 2].
| > Discussion|| |
Since the introduction of mammographic screening programs for breast cancer, the incidence of DCIS has risen constantly. Clear surgical margins have been demonstrated to have direct impacts on local disease control and recurrence rates.,, However, unlike large studies of the risk of recurrence of DCIS,,,,,, the risk factors for positive margins with conservative treatment have been little studied. Furthermore, it is difficult to compare and draw conclusions from the six studies on this topic because of their different methodologies.,,,,, Four of these studies found that positive margins were associated with larger-sized DCIS lesions on mammogram (2.1 cm) and the volume of the resected specimen. Two studies found an association between high-grade DCIS and positive margins., Paradoxically, in a study of 100 patients undergoing conservative surgery for DCIS, Mokbel et al. observed a 55% rate of compromised margins, and the single associated factor was low histological grade.
Among the above risk factors, this study observed that only a lesion size of 1.55 cm or greater on the mammogram increased the risks of a positive margin after conservative surgery and of a mastectomy. The fact that more mastectomies were indicated for these cases might have helped to lower the rates of positive margins. Nearly half of all surgical margins were positive, with this percentage being highest among margins after conservative surgery. These findings are consistent with results in literature, as various studies have shown compromised resection rates ranging from 56% to 72%.,,,
Patients who had a clinical lesion (palpable nodule, papillary discharge, or papillary lesion) and underwent conservative surgery had increased risks of positive margins and of requiring a mastectomy. A study in the United Kingdom in 2013 involving 669 cases of DCIS showed that 9.3% of cases had clinical lesions. The proportion of mastectomies in this group was 59%. In this study, clinical cases made up 19.3% of all cases, with 70.8% of these cases receiving mastectomies. In developing countries, breast cancer is frequently diagnosed at an advanced stage, reflecting the lack of adequate screening programs in these countries.,, A similar situation appears to occur with DCIS, as the proportion of cases with symptoms in this study in Brazil was more than double that found in the United Kingdom. Consequently, the rate of mastectomy was higher as well.
Silverstein et al. demonstrated that in addition to the surgical margins, histopathological characteristics, such as nuclear grade and the presence of comedonecrosis, are important prognostic factors for DCIS recurrence. By contrast, this study did not reveal any association between positive surgical margins and DCIS histopathology, either for a nuclear grade or ER status. The secondary findings showed that negative ER was a risk factor for mastectomy. One explanation for this finding might be that negative ER status is more common in lesions with a higher proliferation index. In the group with larger lesions (≥1.55 cm), the ER was negative in 23.2% of cases, whereas it was negative in 8.5% of cases when the lesions were smaller (<1.55 cm).
The analysis of potential predictive factors for positive margins in DCIS patients showed that lesions with clinical manifestations or that were larger than 1.55 cm on the mammogram had higher risks of positive margins after conservative surgery and of mastectomy. There is an obvious need for larger prospective studies to define those factors that could increase the success of surgical resections for DCIS. We conclude that in many cases, conservative surgery to treat DCIS still does not attain local control of the disease in its full form.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Verbeek AL, Hendriks JH, Holland R, Mravunac M, Sturmans F, Day NE. Reduction of breast cancer mortality through mass screening with modern mammography. First results of the Nijmegen project, 1975-1981. Lancet 1984;1:1222-4.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66.
Román M, Rué M, Sala M, Ascunce N, Baré M, Baroja A, et al.
Trends in detection of invasive cancer and ductal carcinoma in situ
at biennial screening mammography in Spain: A retrospective cohort study. PLoS One 2013;8:e83121.
Schnitt SJ, Allred C, Britton P, Ellis IO, Lakhani SR, Morrow M, et al
. Ductal carcinoma in situ
. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO Classification of Tumours of the Breast. Lyon: IARC, 2012.
Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al.
Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst 2011;103:478-88.
Silverstein MJ, Lagios MD, Groshen S, Waisman JR, Lewinsky BS, Martino S, et al.
The influence of margin width on local control of ductal carcinoma in situ
of the breast. N Engl J Med 1999;340:1455-61.
Solin LJ, Recht A, Fourquet A, Kurtz J, Kuske R, McNeese M, et al.
Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ
) of the breast. Cancer 1991;68:2337-44.
Douglas-Jones AG, Logan J, Morgan JM, Johnson R, Williams R. Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ
of the breast. J Clin Pathol 2002;55:581-6.
Rudloff U, Brogi E, Reiner AS, Goldberg JI, Brockway JP, Wynveen CA, et al.
The influence of margin width and volume of disease near margin on benefit of radiation therapy for women with DCIS treated with breast-conserving therapy. Ann Surg 2010;251:583-91.
Morrow M, Jagsi R, Alderman AK, Griggs JJ, Hawley ST, Hamilton AS, et al.
Surgeon recommendations and receipt of mastectomy for treatment of breast cancer. JAMA 2009;302:1551-6.
Devouge P, Phalippou J, Martin de Beauce S, Kerdraon O, Prolongeau JF, Collinet P, et al.
Reexcision for positive margins in the surgery of ductal carcinoma in situ
: Are there any risk factors? Gynecol Obstet Fertil 2013;41:228-34.
Lynge E, Ponti A, James T, Májek O, von Euler-Chelpin M, Anttila A, et al.
Variation in detection of ductal carcinoma in situ
during screening mammography: A survey within the International Cancer Screening Network. Eur J Cancer 2014;50:185-92.
Cheng L, Al-Kaisi NK, Gordon NH, Liu AY, Gebrail F, Shenk RR. Relationship between the size and margin status of ductal carcinoma in situ
of the breast and residual disease. J Natl Cancer Inst 1997;89:1356-60.
Mai KT, Yazdi HM, Ford JC, Matzinger FR. Predictive value of extent and grade of ductal carcinoma in situ
in radiologically guided core biopsy for the status of margins in lumpectomy specimens. Eur J Surg Oncol 2000;26:646-51.
Mokbel K, Choy C, Leris C, Akbar M, Vinnicombe S, Kessar P, et al.
Predictors of positive margins after local excision of ductal carcinoma in situ
. Am J Surg 2001;181:91-5.
de Roos MA, Groote AD, Pijnappel RM, Post WJ, de Vries J, Baas PC. Small size ductal carcinoma in situ
of the breast: Predictors of positive margins after local excision. Int Surg 2006;91:100-6.
Dillon MF, Mc Dermott EW, O'Doherty A, Quinn CM, Hill AD, O'Higgins N. Factors affecting successful breast conservation for ductal carcinoma in situ
. Ann Surg Oncol 2007;14:1618-28.
Melstrom LG, Melstrom KA, Wang EC, Pilewskie M, Winchester DJ. Ductal carcinoma in situ
: Size and resection volume predict margin status. Am J Clin Oncol 2010;33:438-42.
Sigal-Zafrani B, Lewis JS, Clough KB, Vincent-Salomon A, Fourquet A, Meunier M, et al.
Histological margin assessment for breast ductal carcinoma in situ
: Precision and implications. Mod Pathol 2004;17:81-8.
Sundara Rajan S, Verma R, Shaaban AM, Sharma N, Dall B, Lansdown M. Palpable ductal carcinoma in situ
: Analysis of radiological and histological features of a large series with 5-year follow-up. Clin Breast Cancer 2013;13:486-91.
Akinyemiju TF. Socio-economic and health access determinants of breast and cervical cancer screening in low-income countries: Analysis of the World Health Survey. PLoS One 2012;7:e48834.
Sankaranarayanan R, Swaminathan R, Brenner H, Chen K, Chia KS, Chen JG, et al.
Cancer survival in Africa, Asia, and Central America: A population-based study. Lancet Oncol 2010;11:165-73.
Walters S, Maringe C, Butler J, Rachet B, Barrett-Lee P, Bergh J, et al.
Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: A population-based study. Br J Cancer 2013;108:1195-208.
[Table 1], [Table 2]