Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer

Abstract

Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in elderly patients with endocrine-dependent breast cancer. Four to six months of letrozole as PST is an optimum duration with modest benefits thereafter.

Neoadjuvant endocrine therapy: for whom, for how long?

“…The mean time to fi rst response was 3.9 months and the median time to maximum response 4.2 months. While a third of responders achieved maximum response beyond 6 months of treatment, very few responders were identifi ed after 6 months and none from 8 to 12 months [5]. Together with data from other PET studies, these data reinforce the notion that endocrine therapy takes longer to achieve responses than chemotherapy but that most responders can be identifi ed within the fi rst 4 months of treatment; data also suggest that some patients require longer duration of treatment to achieve the highest benefi t, although for the majority a duration of 6 months seems enough.…”

“…These fi ndings did not hold true in larger adjuvant studies and at the present time there is no reliable biomarker to differentiate response to tamoxifen and aromatase inhibitors, making this a research priority. The major weakness of the study by Llombart Cussac et al [5] is the lack of biomarker evaluation. Only ER and PgR status are reported, with a notion of higher response with higher levels of receptors.…”

Prediction of Response to Aromatase Inhibitors in Breast Cancer

“…Although somewhat arbitrary, length of treatment is based upon (i) allowing sufficient time for treatment to produce meaningful tumour shrinkage in responsive cases and (ii) not persisting with ineffective treatment in resistant tumours. However, recent studies showed that extended treatment may increase the response rates [27][28][29][30]. Moreover, since individual tumours are likely to respond in different time frames, the same time point of response assessment in all may lead to misclassification of response in some.…”

Neoadjuvant endocrine treatment for breast cancer: from bedside to bench and back again?

“…The question of duration has recently been valuably clarified [21][22][23] . Dixon and colleagues 21 found that continuing letrozole beyond the traditional 3-4 months provided additional clinical reduction in tumour size and, consequently, enlarged candidacy for breast-conserving surgery.…”

“…Dixon and colleagues 21 found that continuing letrozole beyond the traditional 3-4 months provided additional clinical reduction in tumour size and, consequently, enlarged candidacy for breast-conserving surgery. Similarly, the small (n = 70) Spanish multicentre, open-label, phase ii trial from Llombart-Cussac and colleagues 22 explored maximal response to letrozole in 70 postmenopausal breast cancer patients (age > 65 years). The trial found a median time to objective response of 3.9 months and a median time to maximum response of 4.2 months, but we note that more than one third of all patients (37.1%) achieved a maximal response only later, within 6-12 months.…”