Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery–A systematic review and meta-analysis

Abstract

Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins. Background Neoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences. Aim To determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC. Methods A systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P- values <0.05 were statistically significant. Results 40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5–3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77–2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87–2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88–8.15] p < 0.00001). Conclusion This is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.

The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma

“…Regarding neoadjuvant therapy in invasive lobular carcinomas, many retrospective studies and meta-analyses report low pathologic complete response, high positive surgical margin, and low clinical response compared to ductal carcinoma, and neoadjuvant therapy is considered a relative contraindication [20][21][22][23][24]. e pathological complete response rate of neoadjuvant therapy varies between 1 and 7.4% in the literature [20,[22][23][24].…”

The Impact of Chemotherapy Prescription on Long-Term Survival Outcomes in Early-Stage Invasive Lobular Carcinoma – A Systematic Review and Meta-Analysis

“…Several translational and clinical research studies have illustrated the chemoinsensitive nature of 'pure' ILC [1,9,33]. Although improved oncological outcomes are typically observed in patients who respond favourably to chemotherapy [34,35], these results are nonrepresentative of ILC disease: Cortazar et al, illustrated that ILC demonstrates poor sensitivity to neoadjuvant chemotherapies (NAC) and no impact on OS outcomes overall [pCR rate in ILC: 7.8%, HR: 0.93 (95% CI: 0.50 -1.70)] [36].…”

“…Furthermore, ILCs are typically indolent (moderate-to-well differentiated) tumours with the propensity to develop strong estrogen and/or progesterone receptor positivity and human epidermal growth factor receptor-2 negativity (ER+/PgR+/HER2-) [5]. Accordingly, ILCs tend to be endocrine responsive [8], chemoinsensitive cancers [9], with surgery combined with multimodal therapeutics proving curative for the majority [1,10,11].…”

“…Loss of CDH1 expression is a renowned cellular hallmark of ILC, with histopathological measurement of the biomarker recommended within expert statements for breast carcinoma workup [16]. Given these unique histological parameters, it is imperative that the multidisciplinary team consider an array of host, tumour, and therapeutic factors when treating patients with ILC disease, for example the propensity for strong responsiveness to endocrine agents combined with reported modest sensitivity to systemic chemotherapy, when compared to patients with other histological subtypes [9]. Despite these differences, there are currently no expert consensus statements or guidelines which focus on optimising systemic therapy specific to lobular histology [17].…”

Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer

“…In addition to frequent bone and liver metastasis, ILC is associated with metastatic dissemination in unusual sites such as peritoneum, gastrointestinaland urinary tract, leptomeninges, skin, orbit and ovaries [12][13][14][15] . Regarding management, ILC is less responsive than IBC-NST tumors to chemotherapy, with low pathological complete response (pCR) rates in the neoadjuvant setting 16 . This may be related to the low proliferation rate in ILC compared to other, grade matched, types of breast cancers.…”