Which patient characteristics drive treatment decisions in elderly patients with early stage hormone receptor–positive breast cancer?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 538-538
Author(s):  
Sacha Satram-Hoang ◽  
Carolina M. Reyes ◽  
Alisha Stein ◽  
Khang Q. Hoang ◽  
Faiyaz Momin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Elderly Patients ◽  
Neoadjuvant Therapy ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Stage I ◽  
Genomic Testing ◽  
Lower Grade ◽  
Risk Of Death ◽  
Hormone Receptor Positive

538 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer (BC). We examined treatment patterns and outcomes associated with adjuvant or neoadjuvant therapy among elderly patients (pts) in the US. Methods: The analysis included 18,470 first primary HR+HER2- BC pts from the linked SEER-Medicare database. Pts were diagnosed with Stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, continuously enrolled in Medicare Parts A/B in the year prior to diagnosis, enrolled in Part D in the year after diagnosis, and underwent BC surgery ≤6 months after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival adjusting for pt characteristics. Date of last follow-up was 12/31/2013. Results: There were 13,670 (74%) pts treated with hormonal therapy +/- chemotherapy and 4,800 (26%) untreated. Compared to treated pts, untreated pts were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity, and less genomic testing for risk of recurrence (p<0.0001). In a multivariate analysis, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of genomic testing was associated with a lower risk of death. The Cox model showed a 48% higher risk of death in untreated compared to treated pts (HR=1.48; 95% CI=1.35-1.61). Even in a subset of 8,967 pts with stage I disease, tumor size <2.0cm and grade 1/2; untreated pts had a 22% higher risk of death compared to treated pts (HR=1.22; 95% CI=1.05-1.41). Conclusions: Patients who are older with favorable disease characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to pts who received adjuvant or neoadjuvant therapy. The unmet need among elderly BC pts remains, suggesting that age should not deter guideline-based therapy. [Table: see text]

scholarly journals Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

2017 ◽  
Vol 167 (3) ◽  
pp. 659-669 ◽  
Author(s):  
Gabe S. Sonke ◽  
Lowell L. Hart ◽  
Mario Campone ◽  
Frans Erdkamp ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Elderly Patients ◽  
Hormone Receptor ◽  
Hormone Receptor Positive

scholarly journals Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Barbara Adamo ◽  
Meritxell Bellet ◽  
Laia Paré ◽  
Tomás Pascual ◽  
Maria Vidal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Statistical Significance ◽  
Stage I ◽  
High Expression ◽  
Luminal A ◽  
Proliferative Effect ◽  
Hormone Receptor Positive ◽  
Metronomic Vinorelbine

Abstract Background The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods Postmenopausal women with untreated stage I–III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. Results Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1–2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (− 73.2%) was superior to both monotherapy arms combined (− 49.9%; p = 0.001) and mVNB (− 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (− 73.2%) was numerically higher compared to LTZ (− 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Conclusions Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. Trial registration NCT02802748, registered 16 June 2016.

scholarly journals Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

Breast Care ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. 315-322 ◽  
Author(s):  
Paul Gaß ◽  
Peter A. Fasching ◽  
Tanja Fehm ◽  
Johann de Waal ◽  
Mahdi Rezai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Hormone Receptor ◽  
Patient Population ◽  
Breast Cancer Patients ◽  
Research Issues ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Background: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Predictive factors of resistance to trastuzumab as neoadjuvant therapy in women with HER2-positive breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 168-168
Author(s):  
Hiromitsu Jinno ◽  
Tomomi Sato ◽  
Maiko Takahashi ◽  
Tetsu Hayashida ◽  
Shigemichi Hirose ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Hormone Receptor ◽  
Direct Sequencing ◽  
Pik3ca Mutation ◽  
Operable Breast Cancer ◽  
Mechanisms Of Resistance ◽  
Her2 Positive ◽  
Pten Loss ◽  
Hormone Receptor Positive

168 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance to trastuzumab is a common clinical phenomenon. However, the mechanisms of resistance to trastuzumab have not been fully elucidated. The objective of this study was to determine the possible mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel plus weekly trastuzumab before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 status did not affect the pCR rate. Although membranous pIGF1-R expression did not affect pCR rate in hormone receptor-positive patients (66.7% vs. 50.0%), hormone receptor-positive patients with positive membranous pIGF1-R tended to show higher pCR rate compared with negative pIGF1-R (41.2% vs. 0%). PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.

Activation of the PI3K/AKT signal transduction pathway is inversely associated with estrogen receptor levels and correlates with survival in hormone receptor-positive Her2/neu-negative breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10588-10588
Author(s):  
A. M. Gonzalez-Angulo ◽  
B. T. Hennessy ◽  
F. Meric-Bernstam ◽  
Y. Lu ◽  
W. F. Symmans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Pik3ca Mutation ◽  
Significant Proportion ◽  
Stage I ◽  
Akt Pathway ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Group 2 ◽  
Group 1

10588 Background: Hormone receptor-positive is the most common subtype of breast cancer. Despite the successes of antihormone therapy alone or combined with chemotherapy, a significant proportion of patients (30–40%) will have primary or acquired resistance to this treatment. There is a need to identify molecular markers to distinguish patients unlikely to benefit from therapy as well as novel targeted therapeutics that increase the response rate. Methods: We used a novel functional proteomics technology, reverse phase protein array (RPPA), to quantify expression and activation of 42 steroid and kinase signaling proteins in 64 hormone receptor-positive-Her2/neu-negative breast cancers from patients with stage I to III tumors managed with non-steroidal aromatase inhibitors ± chemotherapy. Unsupervised clustering analysis was used to molecularly group the tumors. Recurrence-free survival (RFS) was estimated with the Kaplan Meier product limit method and comparison was made using the Log-rank test. Correlation coefficients were used to look at the relationships between two variables. Results: Median age was 57 years (23–79). Sixteen patients (25%) had stage I tumors, 32 (50%) had stage II tumors and 16 (25%) had stage III tumors. There were two well-defined and distinct clusters of tumors: Group 1: ER high (n=25) and Group 2: PI3K/AKT activated (n=39). 3-year RFS estimates were 100% for group 1 and 59% for group 2 (p=0.04). There were thus clear inverse correlations between markers of activation of PI3K pathway and expression of ER (R for pAKT vs ER = -0.26, p=0.03). PIK3CA mutation was detected in 12/58 (21%) of hormone receptor-positive breast cancers and these tumors were found to have a proteomic signature distinct from PTEN loss with the former signature associated with a trend to improved RFS (p=0.06). Conclusion: Activation of the PI3K/AKT pathway in hormone receptor- positive-Her2/neu-negative breast cancer is inversely correlated with ER levels and associated with adverse outcome. At least in some cases, PI3K/AKT pathway activation, may be under the control of genomic aberrations. A validation set of 100 tumors treated with tamoxifen is on- going. No significant financial relationships to disclose.

Clinical relevance of small tumor size (pT1a-b) for patients with HER2-positive, node-negative breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22011-e22011
Author(s):  
G. Curigliano ◽  
L. Fumagalli ◽  
V. Bagnardi ◽  
N. Rotmensz ◽  
M. Locatelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Her2 Overexpression ◽  
Negative Group ◽  
Her2 Positive ◽  
Node Negative ◽  
Positive Group ◽  
Hormone Receptor Positive ◽  
Group 5

e22011 Background: Prognosis of patients with node-negative, HER2-positive disease and tumor size ≤ 1 cm is a matter of controversy. We assessed the prognostic role of HER2 overexpression/amplification in a large series of patients with node-negative, pT1a,b breast cancers. Methods: All consecutive patients with pT1a,b pN0 M0 HER2-positive breast cancer who underwent surgery at the European Institute of Oncology (IEO) from 1995 to 2006 were identified. No patient received trastuzumab in the adjuvant setting. A matched cohort comparison was done using as variables hormone receptor status (positive vs. negative), age at surgery and year of surgery. Comparison group included patients with HER2-negative breast cancer matched 1:1 for hormone receptor negative group and 1:2 for hormone receptor positive group. We estimated rates of local recurrence, distant metastases, disease free survival (DFS) and overall survival (OS) in the hormone receptor positive and hormone receptor negative group. Results: We identified 150 patients with pT1a,b pN0 M0 HER2-positive tumors. The median follow-up was 4.6 years (range 1.0–9.0). In the hormone receptor positive group 5-year DFS was 99% [95% CI: 98%-100%] for HER2-negative and 92% [95% CI: 86%-99%] for HER2-positive disease. In the hormone receptor negative group 5-year DFS was 92% [95% CI: 84%-100%] for HER2-negative and 91% [95% CI: 84%-99%] in HER2-positive disease. Overall, for patients with hormone receptors positive and negative disease, the hazard ratio (HR) associated to HER2 overexpression was 2.4 (95% CI: 0.9–6.5, p=0.09). OS in HER2-positive pT1a,b pN0 M0 breast cancer was similar in hormone receptor positive and negative patients (p=0.93). Conclusions: Node-negative, HER2-positive, pT1a,b breast cancer have a low risk of locoregional and distant recurrence within the first 5 years after diagnosis. In patients with hormone receptor positive, pT1a,b N0 M0 tumors, HER2 overexpression seems to be associated with a dire prognosis (HR=5.2, 95% CI: 1.0–25.9) in terms of DFS. No significant financial relationships to disclose.

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