Neoadjuvant ER-Positive Breast Cancer Chemotherapy Offers Fewer Clinical Benefits for Invasive Lobular Carcinoma than Invasive Ductal Carcinomas

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(ChemotherapyAdvisor) – Neoadjuvant chemotherapy is associated with poorer short-term clinical benefits but equivalent (low) pathological complete response (pCR) for estrogen receptor (ER)–positive) invasive pure lobular breast carcinoma (ILC) compared to ER-positive invasive ductal carcinoma (IDC), according to the largest such analysis published to date. But neoadjuvant chemotherapy might nevertheless offer modest improvements in long-term overall survival for both groups of patients, suggest study findings published online in the British Journal of Cancer.

“Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC,” wrote a team including senior author Lajos Pusztai, MD, PhD, of the MD Anderson Cancer Center at University of Texas in Houston, and Yale Cancer Center in New Haven, CT. “Pathological complete responses are rare in both groups, but do not significantly differ after adjusting for other variables.”

Overall survival at 44 months was similar for ER-positive IDC and ER-positive ILC (hazard ratio [HR] 1.01; 95% CI: 0.7-1.47; P=0.9), they reported.

ILC represents 10% to 15% of all breast cancers and are “almost invariably” ER+, the authors noted. Because its cells have little cytoplasm it can be challenging to palpate or detect with mammography,  resulting in higher rates of tumor cell-positive surgical margins in breast-conserving lumpectomy. Pathological complete response rates following neoadjuvant chemotherapy have been reported to be significantly lower than with IDCs, leading some researchers to conclude neoadjuvant chemotherapy is inappropriate for ILC tumors.

The authors of the new study analyzed data from a total of 1,895 patients with stage 1-3 ER-positive breast cancers (ILC, n=177 and IDC, n=1,718). Patients had undergone neoadjuvant chemotherapy (including anthracycline, anthracycline + taxane, taxane, trastuzumab, hormonotherapy + chemotherapy, or hormonotherapy).

Patients in the ILC group tended to be older and to have larger and lower-grade (grade 1/2) tumors, the authors cautioned.

At a median follow-up of 44 months (range, 1-221 months), 290 patients had experienced tumor recurrence. Tumor downstaging was less frequent in ILC (41%) than IDC (64%; P<0.0001), they noted. Disease-free survival and local recurrence-free survival were also similar for the two groups (P=0.13 and 0.65, respectively).

“Positive or close surgical resection margins were significantly more frequent in ILC patients (19 vs 11%; P=0.001) and this remained significant even after multivariate analysis including tumor size and grade (OR [odds ratio] 1.82; 95% CI: 1.13-2.93; P=0.01),” the authors reported. Breast-conserving surgery was less frequent in ILC patients, as well (19% vs. 34%; P<0.001), they reported. The differences remained significant after adjusting for other clinical variables, including grade and tumor size.

The results “collectively indicate that clinical benefit from neoadjuvant chemotherapy in operable ER-positive ILC is less compared with ER-positive IDC due to the inherently lower chemotherapy sensitivity of these cancers and their unique anatomical features, which makes determination of cancer margins more difficult intraoperatively.”

However, it would be an “oversimplification” to conclude that ILC simply does not respond to neoadjuvant chemotherapy, they emphasized. While most patients with ILC “are unlikely to derive substantial short-term clinical benefit” from neoadjuvant chemotherapy, they may derive modest long-term survival benefits, similar to those seen in ER-positive IDCs, they explained.

Abstract

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