Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm

We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a 'triple-negative' status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.3. Our observation demonstrates that an AR-expressing apocrine breast cancer may respond to androgen deprivation, as an ER-positive breast cancer may benefit from estrogen deprivation. It highlights the importance of further research targeting the AR pathway in apocrine carcinoma, for which androgens represent the sole (known) steroid hormone stimulating tumor growth. Future clinical trials should not only focus on AR inhibitors like enzalutamide, but also on ablative modalities like low-dose hydrocortisone aiming at medical adrenalectomy. This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity.status: publishe

Withdrawal of exogenous hormones might affect multi-gene signature results in early luminal breast cancer

status: publishe

Treatment decision in early stage ER+ HER2− breast cancer without the 70-gene signature test: a retrospective analysis

Aim MINDACT concluded that all breast cancer patients with a high clinical risk using a modified version of Adjuvant! Online need the 70-gene signature test (MammaPrint) to avoid adjuvant chemotherapy (aCT). As such aCT can safely be avoided in 71.5% (1093/1529) women with a high clinical risk grade 1-2 lesion. The aim of this study was to investigate distant recurrence free interval (DRFI) by use of aCT based on demographic and clinicopathological criteria only. Methods In this retrospective study we evaluated patients that were diagnosed in the Multidisciplinary Breast Center in the University Hospitals Leuven between 2000 and 2012. We assessed DRFI by use of aCT in our series of 942 consecutive grade 1-2 lesions with a high clinical risk (<71 years, grade 1, pN0, tumor size 3.1-5cm; <71 years, grade 1, pN1, tumor size 2.1-5cm; <71 years, grade 2, pN0, tumor size 2.1-5cm; <71 years, grade 2, pN1, any tumor size) as in MINDACT. Patients were estrogen receptor (ER) positive, human epidermal growth factor receptor2 (HER2) negative and received adjuvant endocrine therapy. Results In our center, aCT was used based on demographic and clinicopathological criteria only and 550 (58%) of high clinical risk patients did not receive aCT. The median follow-up was 8.2 years. The overall 5-year cumulative DRFI was 2.4% (95% CI, 1.5-3.2); this was 1.7% (95% CI, 0.9-3.1) in those who did not receive and 3.2% (95% CI, 1.8-5.4) amongst those who did receive aCT. Table 1 describes the patients who did not receive and who did receive aCT. Conclusion Omission of aCT based on clinicopathological results, in ‘MINDACT clinical high risk’, ER positive, grade 1-2 tumors, resulted in a low 5-year cumulative DRFI (1.7%). Clinicopathological factors may contribute to the most cost-effective use of gene expression profiles.status: publishe

The UZ Leuven Policy for Extended Adjuvant Anti-estrogen Therapy in Women With Early Estrogen Receptor-Positive Breast Cancer

Opinion statement: Five years after adjuvant endocrine treatment for estrogen receptor (ER)-positive breast cancer, patients have a 2 to 20 % risk of metastatic relapse during the next 5 years. Extended adjuvant endocrine therapy seems to further lower this. In UZ Leuven, extended endocrine therapy is now discussed unless the tumor was a grade 1-2, pT1N0, ER-positive, progesterone receptor (PR)-positive, HER2-negative lesion. After 5 years of adjuvant tamoxifen treatment for ER-positive breast cancer, we encourage women to take another 5 years of tamoxifen. If the tumor was lymph node-positive at diagnosis and patients are menopausal after the first 5 years of tamoxifen, we advise to take prolonged treatment with an oral aromatase inhibitor (AI). For this particular group, available data for extending endocrine therapy with an AI after 5 years of tamoxifen are strongest and more convincing for letrozole than for anastrozole or exemestane. Under these conditions, letrozole is reimbursed for 3 years in Belgium. If women are postmenopausal at diagnosis and already used an oral AI at any time during the first 5 years, we discuss an extra 5 years of tamoxifen. Results from ongoing clinical trials will tell us whether in these cases prolonged AI use is better than tamoxifen so that therapy can be adapted. Benefit from extended adjuvant endocrine therapy is likely larger with better compliance and potential side effects of extended endocrine therapy need to be discussed. Therefore, when advising extended adjuvant endocrine treatment, a balance should always be made between relapse risk and treatment tolerance/compliance.status: publishe

Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer (vol 38, pg 1071, 2018)

Dr. Arteaga serves on an Advisory Board for Novartis and was a consultant for AstraZeneca from 2015 to 2016. All other authors declare that they have no competing interests.status: publishe

Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer

We present the case of a postmenopausal patient with a secondary metastatic ER-positive, HER2-negative breast cancer who was successfully treated with fulvestrant and alpelisib following six lines of therapy. The tumour showed two uncommon PIK3CA mutations, and with the combination of alpelisib and fulvestrant the patient went from ECOG grade 3, before the start of this therapy, to ECOG grade 1 during treatment until progressive disease after 6 months. This unexpected benefit emphasizes the importance of performing a Next Generation Sequencing (NGS)-based assay to screen for several cancer genes in the metastatic setting, even after more than four lines of therapy and a high ECOG grade. Moreover, the use of alpelisib may be beneficial for uncommon PIK3CA mutations.status: publishe

Identification, clinical-pathological characteristics and treatment outcomes of patients with metastatic breast cancer and somatic human epidermal growth factor receptor 2 (ERBB2) mutations.

PURPOSE: The human epidermal growth factor receptor 2 (ERBB2) may harbour somatic mutations that drive breast tumorigenesis. Here, we study prevalence, tumour characteristics and disease outcome of ERBB2 mutations in a large unselected cohort of metastatic breast cancer (mBC) patients. METHODS: We retrospectively included all mBC patients with sufficient primary breast tumour, diagnosed between 2000 and 2015 (n = 775). Genomic DNA was subjected to a targeted-resequencing assay to identify hotspot mutations in exon 8, 17, 19, 20, and 21 of ERBB2. We studied demographics, tumour characteristics, median distant disease-free survival (DDFS), using a time-to-event analysis and time to progression (TTP) and overall survival (OS) upon metastasis, using Kaplan-Meier and log-rank statistics to assess differences between ERBB2-mutation statuses. RESULTS: ERBB2 mutations were observed in 1.8% of the samples (13/721). Patient and tumour characteristics were independent of ERBB2 mutations. Luminal ERBB2-mutated (ERBB2mut+) cases (n = 5) had a shorter DDFS than ERBB2mut- cases (median DDFS 0.8 vs. > 4.0 years, p = 0.02). ER-positive ERBB2mut+ patients who received an aromatase inhibitor (AI) as first-line treatment (stage IV disease) had a worse TTP vs. ERBB2mut- patients (n = 3 vs. 156; median TTP 103 vs. 311 days, p = 0.04). OS for all subtypes was lower for ERBB2mut+ vs. ERBB2mut- cases (n = 11 vs. 669; median OS 1.1 vs. 2.3 years, p = 0.46). CONCLUSION: ERBB2mut+ are rare in patients in whom mBC developed and no evidence was found for an association with specific types of BC or patient characteristics, although outcomes of ERBB2mut+ carriers might be worse. The latter, however, needs to be validated in larger populations.status: publishe

The prognostic performance of Adjuvant! Online and Nottingham Prognostic Index in young breast cancer patients

Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients.status: publishe