Pathologic Response of Associated Ductal Carcinoma In Situ to Neoadjuvant Systemic Therapy: A Systematic Review

Abstract

Contrary to traditional assumptions, recent evidence suggests that neoadjuvant systemic therapy (NST) given for invasive breast cancer may eradicate co-existent ductal carcinoma in-situ (DCIS), which may facilitate de-escalation of breast resections. The aim of this systematic review was to assess the eradication rate of DCIS by NST given for invasive breast cancer. Searches were performed in MEDLINE using appropriate search terms. Six studies (N = 659) in which pathological data were available regarding the presence of DCIS prior to neoadjuvant chemotherapy (NACT) were identified. Only one study investigating the impact of neoadjuvant endocrine therapy (NET) met the search criteria. After pooled analysis, post-NACT pathology showed no residual DCIS in 40.5% of patients (267/659; 95% CI: 36.8-44.3). There was no significant difference in DCIS eradication rate between triple negative breast cancer (TNBC) and HER2-positive disease (45% vs. 46% respectively). NET achieved eradication of DCIS in 15% of patients (9/59). Importantly, residual widespread micro-calcifications after NST did not necessarily indicate residual disease. In view of the results of the pooled analysis, the presence of extensive DCIS prior to NST should not mandate mastectomy and de-escalation to breast conserving surgery (BCS) should be considered in patients identified by contrast enhanced magnetic resonance imaging (CE-MRI).

Keywords: breast cancer; down-staging; ductal carcinoma in-situ; neoadjuvant therapy.

Figure 1

(a) Contrast-enhanced MRI of a 40-year-old woman with a 15 mm invasive breast cancer associated with non-mass enhancement (total footprint 60 mm) confirmed to be high grade DCIS on MRI-guided biopsy. The tumour was HER2 positive. (b) Pre-operative mammogram showing marker clip and SAVI SCOUT reflector. (c) Post-NST contrast-enhanced MRI showing excellent response of both invasive and DCIS components to paclitaxel, transtuzumab & pertuzumab, justifying de-escalation to BCS. (d) Intra-operative specimen mammogram showing radiological marker clip and SAVI SCOUT reflector centrally, with ligaclips for orienting circumferential margins. (e) Post-operative appearance following BCS and adjuvant radiotherapy. Mastectomy was avoided by the down-staging of DCIS by NST.

Figure 1

(a) Contrast-enhanced MRI of a 40-year-old woman with a 15 mm invasive breast cancer associated with non-mass enhancement (total footprint 60 mm) confirmed to be high grade DCIS on MRI-guided biopsy. The tumour was HER2 positive. (b) Pre-operative mammogram showing marker clip and SAVI SCOUT reflector. (c) Post-NST contrast-enhanced MRI showing excellent response of both invasive and DCIS components to paclitaxel, transtuzumab & pertuzumab, justifying de-escalation to BCS. (d) Intra-operative specimen mammogram showing radiological marker clip and SAVI SCOUT reflector centrally, with ligaclips for orienting circumferential margins. (e) Post-operative appearance following BCS and adjuvant radiotherapy. Mastectomy was avoided by the down-staging of DCIS by NST.

Figure 2

Intra-operative specimen mammogram showing residual micro-calcification after NST for triple-positive invasive breast cancer associated with DCIS with orientation staples in situ. The patient had BCS and the final histology confirmed pCR. There was no DCIS associated with the micro-calcifications seen. The patient remains disease-free three years after surgery.

Figure 3

Right oblique mammogram showing extensive micro-calcifications (120 mm) associated with high grade DCIS (ER-negative/HER2-positive) and invasive breast cancer (triple-positive) in a 37-year-old patient. The final histology showed pCR and no viable residual DCIS after NST (chemotherapy and HER2 antibodies). The patient had nipple-sparing mastectomy and immediate reconstruction with targeted axillary dissection. Preservation of the nipple was facilitated by the eradication of extensive DCIS with NST.

Figure 4

(a) 50-year-old patient with 15 mm triple-positive grade two invasive ductal carcinoma in the right upper outer quadrant with extensive biopsy proven DCIS and pleomorphic micro-calcifications within 1 cm of the nipple. (b) MRI showed extensive mass and non-mass enhancement spanning 10 cm. The patient received neoadjuvant weekly Paclitaxel and trastuzumab with pertuzumab for three months. (c) Post-NST MRI showed a complete radiological response. The patient underwent nipple-sparing mastectomy and reconstruction with SLNB. The final histology confirmed pCR and no viable DCIS associated with residual micro-calcifications.