scholarly journals Bridging Endocrine Therapy for HR+/HER2- Resectable Breast Cancer: Is it Safe?

2021 ◽  
pp. 000313482110472
Author(s):  
Kathleen A. Iles ◽  
Madeline Thornton ◽  
Jihye Park ◽  
Mya Roberson ◽  
Philip M. Spanheimer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Care Utilization ◽  
P Value ◽  
Neoadjuvant Endocrine Therapy ◽  
Treatment Protocols ◽  
Exact Test ◽  
Primary Surgery ◽  
Her2 Breast Cancer

Background The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors. Methods Women ≥18 years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher’s exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach. Results Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P-value = .0007), receive surgery sooner (22 vs 29 days, P-value < .001), and within 60 days from diagnosis date (100% vs 85%, P-value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P-value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups ( P-value = .9253). Discussion Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.

scholarly journals Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review

2016 ◽  
Vol 38 (12) ◽  
pp. 615-622 ◽  
Author(s):  
Tomás Reinert ◽  
Susana Ramalho ◽  
Rodrigo Gonçalves ◽  
Carlos Barrios ◽  
Marcia Graudenz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Low Income ◽  
Hormone Receptor ◽  
Urban Areas ◽  
Low Cost ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Breast Cancers ◽  
Neoadjuvant Endocrine Therapy

AbstractBreast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.

scholarly journals Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial

2019 ◽  
Vol 37 (5) ◽  
pp. 386-395 ◽  
Author(s):  
Silvia Dellapasqua ◽  
Kathryn P. Gray ◽  
Elisabetta Munzone ◽  
Daniela Rubino ◽  
Lorenzo Gianni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Premenopausal Women ◽  
Rank Test ◽  
Neoadjuvant Endocrine Therapy ◽  
Endocrine Activity ◽  
Patient Reported ◽  
Premenopausal Patients ◽  
To Receive

PURPOSE To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer. PATIENTS AND METHODS Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2–negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level ≤ 2.72 pg/mL [≤ 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided α of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms. RESULTS Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P < .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and triptorelin plus letrozole were as expected. CONCLUSION In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.

scholarly journals Contralateral parenchymal enhancement on breast MRI before and during neoadjuvant endocrine therapy in relation to the preoperative endocrine prognostic index

2020 ◽  
Vol 30 (12) ◽  
pp. 6740-6748 ◽  
Author(s):  
Max A. A. Ragusi ◽  
Claudette E. Loo ◽  
Bas H. M. van der Velden ◽  
Jelle Wesseling ◽  
Sabine C. Linn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Poor Prognosis ◽  
Prognostic Index ◽  
Good Prognosis ◽  
Response Monitoring ◽  
Neoadjuvant Endocrine Therapy ◽  
Final Pathology ◽  
Her2 Breast Cancer ◽  
Parenchymal Enhancement

Abstract Objectives To investigate whether contralateral parenchymal enhancement (CPE) on MRI during neoadjuvant endocrine therapy (NET) is associated with the preoperative endocrine prognostic index (PEPI) of ER+/HER2− breast cancer. Methods This retrospective observational cohort study included 40 unilateral ER+/HER2− breast cancer patients treated with NET. Patients received NET for 6 to 9 months with MRI response monitoring after 3 and/or 6 months. PEPI was used as endpoint. PEPI is based on surgery-derived pathology (pT- and pN-stage, Ki67, and ER-status) and stratifies patients in three groups with distinct prognoses. Mixed effects and ROC analysis were performed to investigate whether CPE was associated with PEPI and to assess discriminatory ability. Results The median patient age was 61 (interquartile interval: 52, 69). Twelve patients had PEPI-1 (good prognosis), 15 PEPI-2 (intermediate), and 13 PEPI-3 (poor). High pretreatment CPE was associated with PEPI-3: pretreatment CPE was 39.4% higher on average (95% CI = 1.3, 91.9%; p = .047) compared with PEPI-1. CPE decreased after 3 months in PEPI-2 and PEPI-3. The average reduction was 24.4% (95% CI = 2.6, 41.3%; p = .032) in PEPI-2 and 29.2% (95% CI = 7.8, 45.6%; p = .011) in PEPI-3 compared with baseline. Change in CPE was predictive of PEPI-1 vs PEPI-2+3 (AUC = 0.77; 95% CI = 0.57, 0.96). Conclusions CPE during NET is associated with PEPI-group in ER+/HER2− breast cancer: a high pretreatment CPE and a decrease in CPE during NET were associated with a poor prognosis after NET on the basis of PEPI. Key Points • Change in contralateral breast parenchymal enhancement on MRI during neoadjuvant endocrine therapy distinguished between patients with a good and intermediate/poor prognosis at final pathology. • Patients with a poor prognosis at final pathology showed higher baseline parenchymal enhancement on average compared to patients with a good prognosis. • Patients with an intermediate/poor prognosis at final pathology showed a higher average reduction in parenchymal enhancement after 3 months of neoadjuvant endocrine therapy.

scholarly journals NEOADJUVANT ENDOCRINE THERAPY FOR PATIENTS WITH ESTROGEN-RECEPTOR-POSITIVE BREAST CANCER

2018 ◽  
Vol 17 (3) ◽  
pp. 11-19
Author(s):  
V. F. Semiglazov ◽  
V. V. Semiglazov ◽  
G. A. Dashyan ◽  
P. V. Krivorotko ◽  
V. G. Ivanov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Locally Advanced ◽  
Response To Therapy ◽  
Neoadjuvant Endocrine Therapy ◽  
Receive Hormone Therapy ◽  
Study Results ◽  
Estrogen Receptor Positive

More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable  tumors receive adjuvant endocrine therapy. Patients with metastatic  ER+ breast cancer also receive hormone therapy as first-line  treatment. Patients with ER+/PR+ locally advanced breast cancer  including potentially operable cases (cT2N1, cT3N0M0) are still a  subject to neoadjuvant chemotherapy in most of the oncology  centers in Russia and worldwide. More than 10 years ago, several  trials evaluating the efficacy of neoadjuvant endocrine therapy were  conducted in the Petrov Research Institute of Oncology (aromatase  inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs  neoadjuvant chemotherapy, etc.) The primary endpoint was the  evaluation of pathologic complete/partial response to therapy and  the frequency of breast-conserving surgeries following neoadjuvant  treatment. We now represent 10-year long-term follow-up data on  comparison of neoadjuvant chemotherapy with neoadjuvant  endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study  results show tendency to better 10-year disease-free survival in  patients with luminal-A breast cancer who received endocrine  therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9  %, respectively, p=0.062) There were no statistically significant  differences in DFS rates among patients with the luminal B breast  cancer subtype (41 % vs 40 %) The discovery of biomarkers of  potential resistance to endocrine therapy (cycline-dependant kinase  activity [cdk 4/6], estrogenreceptor mutation [ESR1], mTOR  signaling pathway activity, co-expression of the ER and HER2neu  [ER+/ HER2neu3+]) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the  armamentarium of endocrine-therapy for not only metastatic and  locally-advanced but also operable cases of ER+ breast cancer.

scholarly journals Neoadjuvant endocrine therapy in combination with melatonin and metformin in locally advanced breast cancer

2019 ◽  
Vol 30 ◽  
pp. v99-v100
Author(s):  
T.Y. Semiglazova ◽  
M. Osipov ◽  
P. Krivorotko ◽  
S. Protsenko ◽  
V. Semiglazov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Neoadjuvant Endocrine Therapy

Neoadjuvant endocrine therapy with exemestane in locally advanced breast cancer: The initial results from a Brazilian breast cancer center.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 135-135
Author(s):  
F. Marziona ◽  
A. Mattar ◽  
R. Hegg ◽  
S. J. Belloni ◽  
S. B. Rocha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Clinical Response ◽  
Endocrine Therapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Endocrine Therapy ◽  
Initial Results

135 Background: Endocrine therapy is a well-established treatment for hormone-positive breast cancer, both in the adjuvant and the metastatic setting. Neoadjuvant chemotherapy has been used to increase the number of patients who are eligible for breast-conservation therapy (BCT) by inducing tumor downstaging. Neoadjuvant endocrine therapy (NET) is mostly used in patients who are not eligible for chemotherapy (almost reserved to postmenopausal patients). The clinical response with NET in postmenopausal patients with locally advanced breast cancer (LABC) and positive hormonal receptors is almost 75% with aromatase inhibitors (AI). The comparison among tamoxifen and the three AI (anastrozole, letrozole, and exemestane) shows a superiority to AI regarding BCT. There are few data in premenopausal women and NET. Methods: 29 women with rich positive hormone receptor were enrolled in the study between January to September of 2010. Patients received exemestane 25mg/day (EXE) and as we included both pre (12 patients) and postmenopausal (17 patients) women, the premenopausal ones were submitted to ooforectomy. Results: All patients were clinical stage III. In the premenopausal group 6 patients were submitted to surgery and 5 are still taking EXE. Between the two groups 9 patients were submitted to surgery, 4 showed response and are scheduling to surgery, 10 are still taking exemestane. Five patients had serious comorbidities and were submitted to radiotherapy after 9 months of EXE (one without clinical tumor) and are asymptomatic for at least 4 months. Just one patient (premenopausal) had tumor progression after 5 months of EXE and was switched to chemotherapy. Most common side effects were arthralgia/myalgia grade 1/2. Conclusions: In Brazil LABC is frequent and neoadjuvant chemotherapy is the standard treatment. We offered a treatment with a lower cost and especially lower side effects. Because of the initial stage, BCS was not possible, but we had clinical response in about 75% of the patients. This approach was good for patients with comorbidities, and despite the NET is not established for premenopausal patients our initial results encourage us to recommend it.

The effect of trastuzumab on pCR in locally advanced HER2-positive breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 286-286
Author(s):  
S. M. Lavasani ◽  
K. I. Pritchard ◽  
A. Kiss ◽  
S. Verma ◽  
F. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Cancer Center ◽  
P Value ◽  
Her2 Positive ◽  
Primary Tumors ◽  
Her2 Breast Cancer ◽  
Baseline Characteristics

286 Background: Neoadjuvant therapy (NAT) is now standard of care for locally advanced breast cancer (LABC). Evidence shows that pathological complete response (pCR) predicts for disease free and overall survival. The pCR rates for LABC vary widely in the literature but prognosis still remains poor for this group of pts. Increases in pCR have been reported in clinical trials with the addition of trastuzumab (T) but these studies have predominantly included operable pts. The aim of this study was to evaluate whether the addition of T to NAT has improved the rates of pCR in HER2+ LABC pts at our center. Methods: Pts from the LABC prospective database at the Sunnybrook Odette Cancer Center in Toronto were included if they had confirmed HER2+ LABC [primary tumors greater than 5cm (T3) with skin or chest wall involvement (T4) or with matted axillary adenopathy (N2)]. Two cohorts of LABC pts, pre-T and post-T groups were compared for baseline characteristics and pCR. Chi square tests and p values were used for comparing proportions. Results: 43 pts were diagnosed between Jan 2002 to Dec 31, 2006 who had HER2+ breast cancer and received NAT without T (pre-T cohort). 17 HER2+ pts were diagnosed with LABC between Jan 1, 2007 to Dec 31, 2009 who received neoadjuvant T (post-T cohort). Baseline characteristics were similar in two cohorts (Table) except more pts in pre-T cohort received neoadjuvant hormonal therapy. The rate of pCR in the pre-T cohort was 9.3% and in the post-T cohort 29% (p value=0.02). Conclusions: The pCR rate dramatically improved in our LABC patients with the addition of T to NAT. The pCR rates still remain lower than in published clinical trials likely reflecting the more advanced nature of LABC in clinical practice. [Table: see text]

Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine resistant HER2-/HR+ breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1148-TPS1148
Author(s):  
Fabrice Andre ◽  
Richard Greil ◽  
Neelima Denduluri ◽  
Alejandro Javier Yovine ◽  
Cathy Reddick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Phase Ii ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Predictive Biomarkers ◽  
Her2 Breast Cancer ◽  
Patient Reported

TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients (pts) have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy but can be overcome via FGFR1 inhibition in preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor tyrosine kinase inhibitor that demonstrated antitumor activity in heavily pretreated breast cancer pts with FGF pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and is studied here to determine if it can improve outcomes when combined with fulvestrant. Methods: Postmenopausal HER2-/HR+ locally advanced or metastatic breast cancer pts (N»150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting will be enrolled in this multicenter, randomized, double blind, placebo controlled, phase II trial. Pts will prospectively undergo molecular screening to enrich for FGF-amplification (FGFR1, FGFR2, or FGF3 amplification by qPCR; 45 amplified and 30 non-amplified pts per arm). Pts will be randomized 1:1 to receive fulvestrant (500 mg q4w [with an additional dose 2 wks after the initial dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or placebo until disease progression, unacceptable toxicity, or death. The primary endpoint is progression-free survival, with tumor assessments performed q8w. Secondary endpoints include overall response rate per RECIST v1.1, duration of response, overall survival, ECOG performance status and patient reported outcome scores over time, and safety. The pharmacodynamic effect of dovitinib on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to dovitinib will be explored.

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