Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer

Abstract

Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2 -4 N0 -1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (Po0.0001). Higher Ki-67 proliferation indices were associated with PgRÀ tumours (median 28.3%, PgR þ 22.9%; P ¼ 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P ¼ 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying 475% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P ¼ 0.004).

Change in the hormone receptor status following administration of neoadjuvant chemotherapy and its impact on the long-term outcome in patients with primary breast cancer

“…The overall frequency of patients with HR status conversion was 16.0%. This incidence of HR status conversion was similar to previous reports on post-NAC change in the ER, PgR, and HER2 statuses, which reported incidences of 8 -28%, 6 -59% (Bottini et al, 1996;Lee et al, 2003;Taucher et al, 2003;Colleoni et al, 2004;Burcombe et al, 2005;Shet et al, 2007;Kasami et al, 2008;Neubauer et al, 2008), and 0 -21% (Bottini et al, 1996;Colleoni et al, 2004;Arens et al, 2005;Burcombe et al, 2005;Quddus et al, 2005;Adams et al, 2008;Kasami et al, 2008;Neubauer et al, 2008), respectively. Although the rate of cases with no change in the HR status after NAC was high, the incidence of change in the HR status is clinically not negligible.…”

“…The hormone receptor (HR) status is one such factor. Although this status is known to change after NAC (Bottini et al, 1996;Lee et al, 2003;Taucher et al, 2003;Colleoni et al, 2004;Burcombe et al, 2005;Shet et al, 2007;Tacca et al, 2007;Kasami et al, 2008;Neubauer et al, 2008), its impact on long-term outcomes has not been assessed. The objective of this retrospective study was to evaluate the frequency and impact of change in the HR status (HR status conversion) on the long-term outcomes in the NAC-administered breast cancer patients.…”

Serial Changes in Expression of Proteins in Response to Neoadjuvant Chemotherapy in Breast Cancer

“…after neoadjuvant chemotherapy was reported in several studies (112)(113)(114). In general, studies that reported a good concordance of hormone receptor status before and after neoadjuvant chemotherapy had a relatively smaller number of patients compared to the studies that found significant changes.…”

Evaluation of ERα, PR and ERβ isoforms in neoadjuvant treated breast cancer

“…Several research groups observed significant changes in expression levels of tumour parameters like ER·, PR or Her-2 during PST (15)(16)(17)(18)(19)(20)(21)(22)(23). Therefore, it is strongly recommended that hormone receptor expression and other biological markers should be re-evaluated after PST in order to make sure that post-surgery treatment is tailored adequately.…”