Changes in the Tumor Grade and Biological Markers in Locally Advanced Breast Cancer after Chemotherapy ? Implications for a Pathologist

Abstract

There is insurgence of literature evaluating prognostic and predictive factors in breast carcinomas treated with chemotherapy, with a parallel need to develop guidelines for the pathologist interpreting such excisions. Prechemotherapy gun biopsy and postchemotherapy excision specimens from 78 women with locally advanced breast cancer were analyzed for histological changes in the tumor, changes in the tumor grade, hormone receptors, cerb2, and bcl2 and their impact on disease-free survival (DFS). An unusually prominent granulomatous response to tumor was seen in three cases. The tumor grade changed in five patients, estrogen receptor (ER) expression was altered in 10 cases, progesterone receptor detection changed in 16 cases, cerb2 in one case and bcl2 in 16 cases. Fixation of the gun biopsy in Bouin's fluid and severe damage of nuclei after chemotherapy were the reasons for shift in the expression of hormone receptors. A low-grade tumor was associated with better response to chemotherapy. In the Kaplan-Meier analysis the ER expression and a low-grade tumor (grade I and II) significantly affected DFS. None of the factors evaluated impacted the overall survival of patients. To conclude there is a change in the tumor grade, bcl2, cerb2 and hormone receptors after chemotherapy. A pathologist interpreting specimens of breast cancer after chemotherapy must always record the postchemotherapy grade as it is an indicator of better response to chemotherapy and survival.

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.…”

Receptor Status Change From Primary to Residual Breast Cancer After Neoadjuvant Chemotherapy and Analysis of Survival Outcomes

“…Some studies that used IHC to measure HER2, HER2 status changed in 7.6% to 30.0% of tumors after NCT. 8,[18][19][20][21][22][23][24][25][26] A prospective study that used gene amplification to determine HER2 status found that up to 43% of trastuzumab-treated patients had tumors that had HER2 status discordance after NCT. 27 Similarly, we found that 45.7% of the trastuzumab-treated tumors became HER2-negative.…”

Biomarker discordance pre and post neoadjuvant chemotherapy in breast cancer

“…Table 1 summarizes some of the published data looking at hormone receptor discordance in this setting. For estrogen receptor status, discordance rates ranging from 2% to up to 57% were observed while that for progesterone receptor discordance ranges from 5.9% to 51% was observed [23][24][25][26][27][28][29][30][31][32][33]. The question that arises is whether the discordance observed is similar among patients who do and do not receive neoadjuvant chemotherapy.…”

“…Table 2 summarizes some of the published studies looking at changes in Her2 status following a course of neoadjuvant chemotherapy. Studies looking at patients who received neoadjuvant chemotherapy without trastuzumab reported discordance in Her2 ranging from 2.3% to 35% when Her2 was tested by IHC and from 2% to 13% when FISH testing determined Her2 status [23,25,28,[30][31][32][33][39][40][41]. Studies that looked at the discordance of Her2 when trastuzumab was incorporated into the neoadjuvant regimen have reported discordance rates of up to 43% when FISH testing determined Her2 status [42][43][44].…”