Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial

Abstract

Background: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment.

Aims: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer.

Materials/methods: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression.

Results: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly.

Conclusions: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.

Figure 1

Kaplan–Meier estimates of recurrence free survival according to treatment arm for oestrogen receptor positive cases of (A) invasive ductal carcinomas (n  =  274) and (B) invasive lobular carcinoma (n  =  33). TAM, tamoxifen treated.

Figure 2

Kaplan–Meier estimates of recurrence free survival according to treatment arm for oestrogen receptor positive cases with (A) low, (B) intermediate, and (C) high Ki-67 expression. TAM, tamoxifen treated.

Figure 3

Kaplan–Meier estimates of breast cancer survival according to treatment arm for oestrogen receptor positive cases with (A) low, (B) intermediate, and (C) high Ki-67 expression. TAM, tamoxifen treated.