Is histology (His) relevant in adjuvant (Adj)/neoadjuvant (NA) therapy of breast cancer (BC)?

Abstract

10541 Background: Invasive lobular carcinoma (ILC) constitutes 10–15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). Methods: We reviewed the literature to evaluate the effect of His on outcome of Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; 11 compared CT regimens, 3 regimens that contained CT and hormone therapy (HT), and 2 HT only. None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 patients (PTS) showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P < 0.01). Of 39 phase III RT of Adj CT, 7 compared CT vs HT, 14 CT vs CT + HT, 11 HT vs HT + CT, and 7 CT vs HT vs CT + HT. Of the 39 RT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS participating in these 4 RT were ILC), but none analyzed results according to His. Conclusions: We suggest that the role of CT in early ILC is not clear. The pCR rate is significantly lower in ILC PTS treated with NA CT. It is also not clear if His is an independent predictive factor or a marker of grade/ER expression. The specific value of CT in the Adj treatment of ILC PTS has not been adressed in the Adj RT. Past and current, ongoing RT of Adj CT do not stratify PTS according to His neither evaluate the results according to His. Given the potential therapeutic implications, we suggest that the role of His should be more thoroughly investigated in future RT in order to define the appropriate effectiveness of CT and HT in the treatment of ILC PTS, so that possible overtreatment of ILC PTS with CT might be avoided. No significant financial relationships to disclose.