Journal of Clinical & Experimental OncologyISSN: 2324-9110

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Editorial, J Clin Exp Oncol Vol: 2 Issue: 1

Ductal Carcinoma In-Situ: An Editorial

Kelly Lambert1,2 and Kefah Mokbel1*
1The London Breast Institute, The Princess Grace Hospital, London, UK
2The Breast Unit, University Hospitals Leicester, Leicester, UK
Corresponding author : Kefah Mokbel
London Breast Institute, The Princess Grace Hospital, 45 Nottingham Place, London, W1U 5NY, UK
Tel: 0044 (0)207 908 2040; Fax: 0044 (0)207 908 2275
Email: [email protected]
Received: November 08, 2012 Accepted: November 09, 2012 Published: November 16, 2012
Citation: Lambert K and Mokbel K (2012) Ductal Carcinoma In-Situ: An Editorial. J Clin Exp Oncol 2:1. doi:10.4172/2324-9110.1000e107

Abstract

Ductal carcinoma in-situ (DCIS) is an increasingly common pre-invasive form of breast-cancer. 27% of all new breast cancer diagnoses in 2008 in the United States were DCIS as opposed to less that 1% before the introduction of national mammographic screening programmes. It is probably the pre-cursor of most invasive breast-cancer but not all DCIS will progress to this stage. So the challenge in the modern treatment of DCIS is to avoid over-treatment.

Keywords: Ductal carcinoma

Ductal carcinoma in-situ (DCIS) is an increasingly common pre-invasive form of breast-cancer. 27% of all new breast cancer diagnoses in 2008 in the United States were DCIS as opposed to less that 1% before the introduction of national mammographic screening programmes [1].
It is probably the pre-cursor of most invasive breast-cancer but not all DCIS will progress to this stage. So the challenge in the modern treatment of DCIS is to avoid over-treatment.
Historically, DCIS presented incidentally or with a breast mass or nipple discharge. Post introduction of screening it now more commonly presents as asymptomatic calcifications seen on mammography. We know that this latter group have lower rates of local-recurrence after treatment [2,3] and so a proportion of these cases may be less clinically relevant [4]. The question of overtreatment in screening cases has been brought into sharp focus recently by a significant analysis published in the Lancet [5].
Integral to the successful management of DCIS, is surgery to remove the disease with clear margins [6] (this may involve breast conservation or mastectomy with or without reconstructive techniques). Breast radiotherapy and hormonal treatments are also given as adjuvants where appropriate but can these be safely omitted in certain cases?
Treated DCIS has an excellent overall prognosis and so differences in survival have been difficult to demonstrate even in large trials. Differences in local-recurrence rates have been used as a surrogate marker for survival. Radiotherapy was shown to reduce local recurrence in early breast-cancer in 1995 [7] and to be indirectly associated with improved survival in 2005, in that one death was prevented for every four local-recurrences avoided [8]. A direct improvement in overall survival in early breast-cancer attributable to radiotherapy of around one sixth has since been demonstrated [9].
An analysis of long term data on patients treated for DCIS from the NSABP B-17 and NSABP B-24 trials [10] showed that at 15 years, the radiotherapy treated patients had significantly fewer localrecurrences and that this effect increased over time. Of those that did recur 54% were invasive, and for these patients overall survival was lower (HR of death = 1.75, 95% CI = 1.45 to 2.96, P<0.001).
An analysis of the major DCIS trials from the nineties showed that radiotherapy halves the local recurrence rate, producing an absolute reduction in local recurrence at 5 years of 10% and of 15% at 10 years and this benefit is preserved for lower risk cases [11].
The UK/ANZ DCIS trial assessed the effect of adjuvant treatment with Tamoxifen after breast conserving surgery and radiotherapy for DCIS. After a median of 12.7 years follow-up [12], a significant reduction in local recurrence and contra-lateral tumours in Tamoxifen treated patients was seen (HR 0·71, 95% CI 0·58–0·88;p=0·002). Trials are ongoing to determine if Aromatase inhibitors are superior to Tamoxifen in the adjuvant setting after breast conserving surgery for DCIS (NSABP B-35 and IBIS II).
So, there is significant potential benefit overall for patients with DCIS from adjuvant treatments, but given the very good overall prognosis of this condition, patients with a low risk of local-recurrence are likely to be those in which adjuvant treatments could be omitted. Tumour size and grade, the presence or absence of inflammatory changes or necrosis and the ‘comedo’ sub-type (high-grade, central confluent necrosis and solid architectural pattern in >50% of the duct spaces) have been found to be statistically associated with the risk of local recurrence in an independent pathological review of cases from the UKCCCR/ANZ DCIS trial [13]. Margin width was the most significant factor associated with local-recurrence in a large meta-analysis [6]. These factors in isolation are not enough to safely omit adjuvant treatments or to validate less extensive surgery but in combination may be useful.
The Van Nuys index uses a combination of factors that are known to influence local-recurrence rates (size of tumour, grade and margin width at operation) to generate a score. Low recurrence rates have been reported after breast conserving surgery even in the absence of radiotherapy with the lowest Van Nuys scores [14] and this index is being used to guide treatment decisions.
Oncotype-DX-DCISTM is a genomic assay that aims to guide radiotherapy decisions in DCIS by generating a score which predicts the likelihood of local-recurrence [15]. This score was validated using tissue and recurrence outcomes from the ECOG 5194 study which included patients treated with BCS alone [16].
It is regrettable that a common condition with such a good general prognosis is so variable in its clinical implications. Thankfully, ongoing research (such as that outlined above) will continue to help us answer the uncertainty that remains in trying to best treat patients with DCIS while minimising harm.

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