The Journal of Steroid Biochemistry and Molecular Biology
Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy☆
Introduction
Primary systemic or neoadjuvant treatment for breast cancer is given with the primary tumours still present in situ within the breast. This form of therapy offers several advantages to the patient in that large tumours may be down-staged following successful treatment allowing more conservative surgery [1] and knowledge of tumour sensitivity to agents which may be subsequently used in an adjuvant setting, can be more precisely assessed by monitoring the volume/size of the primary tumour [2]. Additionally, however, the relatively easy access to tumour within the breast makes sequential sampling possible so that the effects of treatment on tumour biology and histopathology may be followed [3], [4]. In the present study the effect of new aromatase inhibitors (anastrozole/letrozole) given neoadjuvantly have been assessed on clinical/pathological response and histological expression of Ki67 and progestogen receptors in primary breast cancers from postmenopausal women; these have been compared with the effects of tamoxifen given in a neoadjuvant setting to another cohort of patients.
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Patients
Postmenopausal patients with large (>3 cm) oestrogen receptor-positive (>20 fmol/mg cytosol protein or 80 histoscore) primary breast cancers (staged as T2, T3, T4b, N0 or N1, M0) were entered into the study. None had received prior treatment with hormonal agents for breast cancer or were taking hormone preparations at the time of study. Tumour size was monitored clinically (by calipers) and by breast ultrasound before and at monthly intervals during treatment. All patients received primary
Clinical response
Tumour volumes were measured monthly by ultrasound in 24 patients receiving letrozole and 23 women taking anastrozole. Over the same time period 65 women were recruited to treatment with neoadjuvant tamoxifen. Clinical response as assessed by % reduction in tumour volume over 3 months is depicted in Table 1. All drug regimes were capable of producing measurable tumour shrinkage (>25% reduction in tumour volume) in most cases. Furthermore major tumour shrinkage (>50% reduction in volume) was
Discussion
The present study confirms the efficacy of two third-generation aromatase inhibitors (anastrozole and letrozole) when given neoadjuvantly to treat ER-rich breast cancer [8], [9], [10]. The results also highlight differences between aromatase inhibitors and tamoxifen when given in the same setting.
It was possible to demonstrate tumour volume reduction as assessed by ultrasound in most cases, irrespective of the nature of the endocrine agents (volume reduction >25% were seen in 87 and 98% of
References (10)
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Cited by (51)
Neoadjuvant treatment of endometrial cancer using anastrozole: A randomised pilot study
2013, Gynecologic OncologyCitation Excerpt :This study showed a marked decrease in ki-67 scores in the anastrozole arm even as early as 11 days after treatment. This effect is similar to that observed in patients with BC following treatment with aromatase inhibitors [31,34,37–39]. Although a reduction in ki-67 scores was not found to be predictive of clinical response [38], higher ki-67 scores compared to baseline after 2 weeks of treatment with a therapeutic agent were associated with poorer recurrence-free survival in BC patients [40].
Pathology Considerations in Patients Treated with Neoadjuvant Chemotherapy
2012, Surgical Pathology ClinicsCitation Excerpt :For PgR, changes from a positive to a negative result occur more commonly than seen for ER. This is particularly marked after aromatase inhibitor treatment, as reported in 2 studies in which 70% and 94% of cancers lost PgR expression.53,54 In contrast, fewer than 10% of tamoxifen treated cancers lost PgR expression and some cancers had an increase in the degree of positivity.
Clinical, pathological, proliferative and molecular responses associated with neoadjuvant aromatase inhibitor treatment in breast cancer
2010, Journal of Steroid Biochemistry and Molecular BiologyTissue estradiol is selectively elevated in receptor positive breast cancers while tumour estrone is reduced independent of receptor status
2009, Journal of Steroid Biochemistry and Molecular Biology
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Proceedings of the Symposium: ‘Aromatase 2000 and the Third Generation’ (Port Douglas, Australia, 3–7 November 2000).