PracticeUpdate: Haematology & Oncology

ECCO2017 15

More knowledge needed onmolecular subtypes of ER positivity in metastatic breast cancer R esults of a single-centre retrospective study have shown that most subgroups of patients with metastatic breast

receptor-positive breast cancer except in cases of visceral crisis. The implementation of guidelines is variable, however. We wanted to explore response patterns in a consecutive population, to assess the value of endocrine therapy and identify subgroups with more or less benefit from endocrine therapy. All patients who had been treated for oestrogen- and/or progesterone receptor- positive, distant metastatic disease during the prior 15 years were identified and tumour data, treatments, and responses were recorded. In most cases, oestrogen and progesterone receptor, as well as HER2 assessments were performed in the metastasis, but in these cases, status of the primary tumour was used. A total of 246 patients with oestrogen and/or progesterone-positive disease were identified. Most patients had received palliative endocrine treatment and chemotherapy sequentially, but 72 had been treated with hormonal agents only. Thirty-five patients had never received endocrine therapy. Time to treatment failure for each endocrine regimen was calculated and summoned for each patient to receive a cumulative response time to endocrine therapy. Histological grade and type of primary tumour, oestrogen and/or progesterone receptor and HER2 status, site of presenting metastases, and patient age at diagnosis were then correlated with the radiotherapy result. Response to treatment was defined as partial regression or stable disease after more than 3 months of therapy. A total of 206 patients had received one to six different endocrine regimens. Eighty-five percent of patients responded to treatment for 3–250 months, median 27 months. Thirty-two patients responded to endocrine treatment, 26 of whom exhibited strong or medium expression of oestrogen receptors. Three groups of patients responded at 100% to endocrine therapy; grade 1, mucinous and tubular mixed tumours. Median age of patients who received endocrine and chemotherapy sequentially was 54 years. Of those who received endocrine therapy only, median age was 65 years. Patients 40 years of age or younger at the time of diagnosis, at 88%, responded as well as those older than 60 years. HER2-amplified tumours responded at 75% to endocrine therapy without trastuzumab. Maximum response time was 154 and median 34 months. Only two subgroups performed significantly worse than others.

An important finding is that fast-proliferating grade 3 cancers and young patients respond very well to endocrine therapy as well as HER2-positive patients.

cancer who were positive for oestrogen and/ or progesterone receptors responded well to endocrine therapy. Only three small groups, however, responded at 100%. These findings point to a need for more knowledge of molecular subtypes of oestrogen receptor positivity in metastatic breast cancer. Marie Sundqvist, MD, of the Kalmar County Breast Unit, Sweden, explained that patients with oestrogen/progesterone receptor- positive, distant metastatic breast cancer often, but not always, respond to endocrine treatment. Also, the time to treatment failure varies widely. Dr Sundqvist set out to determine whether predictive factors of response to endocrine therapy could be identified from tumour and patient characteristics. Dr Sundqvist said, “Guidelines recommend endocrine therapies as first-line treatment in metastatic, oestrogen and/or progesterone

Patients with oestrogen receptor-negative, progesterone receptor-positive tumours experienced a 56% response rate and those presenting with liver metastasis, a 50% response rate. Median response time for both cohorts was only 6 months. Dr Sundqvist said, “We also compared patients who received endocrine therapy and chemotherapy sequentially. The median cumulated response time to chemotherapies was less than that to endocrine therapies, as was the maximum response time”. “For instance,” she added, “the cumulated response time to endocrine therapies for grade 3 (fast proliferating) tumours was 23 months and maximum response time 81 months, while response to chemotherapies was 12 and 66 months, respectively. The more slowly proliferating grade 1 tumours responded at median of 43, maximum 215 months, to endocrine therapies but only 12 and 24 month, respectively, to chemotherapies.” Dr Sundqvist said that, although most patient subgroups responded well to endocrine therapy, only three small groups responded at 100%. To optimally tailor endocrine treatment in metastatic breast cancer, more knowledge of the molecular subtypes of oestrogen receptor positivity is needed. The results support the assertion that patients presenting with hepatic metastasis and those with oestrogen receptor-negative, progesterone receptor-positive tumours should not receive endocrine therapy as their first line of treatment. “An important finding,” said Dr Sundqvist, “is that fast-proliferating grade 3 cancers and young patients respond very well to endocrine therapy as well as HER2-positive patients.” She added, “Hopefully in the future, studies of the molecular biology of metastases will enable more exact identification of which tumours will vs will not respond to endocrine therapy.”

PracticeUpdate Editorial Team

© ECCO2017 European Cancer Congress

VOL. 2 • NO. 2 • 2017