Adjuvant and neoadjuvant therapy of ER+ / HER2– breast cancer

2021 ◽  
Vol 1 (31) ◽  
pp. 7-12
Author(s):  
V. F. Semiglazov ◽  
M. A. Dzhelialova
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Endocrine Therapy ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Mtor Inhibitors ◽  
Tumor Grade ◽  
Ki 67 ◽  
Her2 Breast Cancer ◽  
Adjuvant And Neoadjuvant Therapy

Even early-stage breast cancer is a heterogeneous disease, so the optimal treatment depends on the pathological characteristics of the tumor. The vast majority of breast tumors (80%) are classified as estrogen receptor positive (ER+) with varying degrees of ER expression. The benefit of endocrine therapy is small with low ER staining (1–10%), occurring in less than 2% of all cases of ER+ breast cancer. Genetic analyzes are valuable for administration of adjuvant chemotherapy prior to endocrine therapy in ER+ / HER2– pN0–pN1c breast cancer. But such tests are not yet widely available. In practical work, when planning adjuvant and neoadjuvant therapy for patients with ER+ / HER2– breast cancer, pathological assessment of the expression of ER, PR, Ki‑67, as well as the tumor grade (G) remains important. The use of drugs to overcome resistance to endocrine therapy: PI3-kinase inhibitors (taselisib), CDK 4/6 inhibitors (palbociclib, abemaciclib, ribociklib), mTOR inhibitors (everolimus) can enhance the effect of neoadjuvant and adjuvant endocrine therapy.

Adjuvant treatment decision in patients with node-negative, ER+/Her2-, early stage breast cancer with Oncotype DX (ODX) recurrence score (RS) of 11-30: Impact of clinicopathologic features.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12022-e12022
Author(s):  
Gwenalyn Garcia ◽  
Shiksha Kedia ◽  
Nishitha Thumallapally ◽  
Elias Moussaly ◽  
Saqib Abbasi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prospective Trial ◽  
Recurrence Score ◽  
Clinicopathologic Features ◽  
Node Negative ◽  
Her2 Breast Cancer ◽  
Node Negative Breast Cancer

e12022 Background: The ODX RS predicts the risk of distant recurrence and the benefit of adjuvant chemotherapy (CT) in patients with ER+/Her2- breast cancer. High RS predicts a large benefit whereas low RS predicts minimal benefit from CT. A prospective trial showed that patients with low RS of 0-10 may be safely spared adjuvant CT. Recommendations in patients with intermediate RS are less clear. We performed a retrospective study of adjuvant therapy decision in patients with RS 11-30. Methods: We identified patients with ER+/Her2-, node-negative breast cancer with ODX RS 11-30 treated at our center from 2010-2016. Data on patient age, type of surgery, tumor size, grade, lymphovascular invasion (LVI), RS and treatment were collected. Statistical associations were tested using Chi square/Fisher's exact test and t test. Logistic regression analysis was used to determine odds ratios (OR). Results: 76 patients were identified. 86% (65/76) of them received adjuvant endocrine therapy alone and 14% (11/76) received adjuvant CT plus endocrine therapy. Patient characteristics are shown in the table. Using univariate analysis, significant predictors of receiving CT included RS, LVI, and ER positivity. In the patients who received CT, RSs were all ≥ 18 whereas in the group who did not receive CT, 42% (27/65) patients had RS 11-17. Increase in RS was associated with increase in the likelihood of receiving CT (OR 1.40, 95% CI 1.14-1.74, p=0.00017). Decrease in ER positivity was correlated with increased likelihood of receiving CT (OR 0.922, 95% CI 0.856-0.992, p=0.03). The presence of LVI increased the likelihood of receiving CT (OR 26.24, 95% CI 4.16-165.43, p=0.0005). Conclusions: In patients with ER+/Her2-, node-negative breast cancer with RS 11-30, the majority received endocrine therapy alone. RS and some clinicopathologic features (LVI, ER) impacted the decision to receive CT. [Table: see text]

scholarly journals 18F-fluorodeoxyglucose (FDG) PET or 18F-fluorothymidine (FLT) PET to assess early response to aromatase inhibitors (AI) in women with ER+ operable breast cancer in a window-of-opportunity study

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Perrin E. Romine ◽  
Lanell M. Peterson ◽  
Brenda F. Kurland ◽  
Darrin W. Byrd ◽  
Alena Novakova-Jiresova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Early Stage ◽  
Early Response ◽  
Window Of Opportunity ◽  
Ki 67 ◽  
Flt Pet ◽  
Post Therapy

Abstract Purpose This study evaluated the ability of 18F-Fluorodeoxyglucose (FDG) and 18F-Fluorothymidine (FLT) imaging with positron emission tomography (PET) to measure early response to endocrine therapy from baseline to just prior to surgical resection in estrogen receptor positive (ER+) breast tumors. Methods In two separate studies, women with early stage ER+ breast cancer underwent either paired FDG-PET (n = 22) or FLT-PET (n = 27) scans prior to endocrine therapy and again in the pre-operative setting. Tissue samples for Ki-67 were taken for all patients both prior to treatment and at the time of surgery. Results FDG maximum standardized uptake value (SUVmax) declined in 19 of 22 lesions (mean 17% (range −45 to 28%)). FLT SUVmax declined in 24 of 27 lesions (mean 26% (range −77 to 7%)). The Ki-67 index declined in both studies, from pre-therapy (mean 23% (range 1 to 73%)) to surgery [mean 8% (range < 1 to 41%)]. Pre- and post-therapy PET measures showed strong rank-order agreement with Ki-67 percentages for both tracers; however, the percent change in FDG or FLT SUVmax did not demonstrate a strong correlation with Ki-67 index change or Ki-67 at time of surgery. Conclusions A window-of-opportunity approach using PET imaging to assess early response of breast cancer therapy is feasible. FDG and FLT-PET imaging following a short course of neoadjuvant endocrine therapy demonstrated measurable changes in SUVmax in early stage ER+ positive breast cancers. The percentage change in FDG and FLT-PET uptake did not correlate with changes in Ki-67; post-therapy SUVmax for both tracers was significantly associated with post-therapy Ki-67, an established predictor of endocrine therapy response.

CDK4/6 Inhibitors: Paving the Way for HR-Positive, HER2-Negative Early Breast Cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Kristi Orbaugh, RN, MSN, RNP, AOCN ◽  
Val R. Adams, PharmD, FCCP, BCOP, FHOPA ◽  
Theresa W. Gillespie, PhD, MA, RN, FAAN
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Free Survival ◽  
Her2 Breast Cancer ◽  
Oral Agents

Cyclin-dependent kinase (CDK) 4/6 inhibitors are revolutionizing care for patients with advanced and metastatic hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2–) breast cancer. These oral agents, often combined with other hormone-based therapy, have demonstrated considerable success in clinical trials and are used widely in oncology practices. CDK4/6 inhibitors are also being investigated for the treatment of early stage HR+, HER2– breast cancer. The addition of abemaciclib to adjuvant endocrine therapy improved invasive disease-free survival and distant relapse-free survival compared with endocrine therapy alone in patients with HR+, HER2–, node-positive, high-risk early breast cancer, and is now FDA-approved as adjuvant treatment in this setting. Here we review recent clinical data supporting the use of CDK4/6 inhibitors in both early and metastatic breast cancer. In addition, an expert faculty panel will discuss practical strategies to promote and improve adherence and side effect management in patients being treated with oral CDK4/6 inhibitors.

scholarly journals Comparison of the Mutation Profiles of Triple-Negative Breast Cancers and Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers at the T2N0-1M0 Stage

2020 ◽  
Author(s):  
Seungju Lee ◽  
Hyun Yul Kim ◽  
Youn Joo Jung ◽  
Hyun-June Paik ◽  
Chang Shin Jung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Tumor Grade ◽  
Breast Cancers ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Epidermal Growth

Abstract BackgroundTriple-negative breast cancer (TNBC) has higher loco-regional recurrence and visceral metastasis compared to other breast cancer subtypes; however, little is known about the molecular pathogenesis and therapeutic targets of TNBC. Therefore, we compared the mutation profiles of early TNBC with those of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) breast cancer using a customized next-generation sequencing capture panel.MethodsDNA was obtained from the primary tumor tissues of 34 patients diagnosed with pT2N0-1M0 HR+/HER2 breast cancer or TNBC. To enrich the 48 breast cancer-associated genes, 21,192 probes were designed using the SureSelect design tool. After library preparation using the SureSelect XT kit (Agilent), paired-end DNA sequencing was performed on a HiSeq platform (Illumina). The mean depth of the target regions was 1,766 (×). The subsequent output containing genetic variation was analyzed using a pipeline of bioinformatics tools. Significant mutations with allele frequencies of more than 30% were checked for their germline counterparts in the peripheral blood. Circulating cell-free nucleic acids were extracted and analyzed with a therascreen® PIK3CA RGQ PCR kit (QIAGEN).ResultsSignificant mutations were found in TP53, PIK3CA, AR, BRCA1, PTEN, BRCA2, BRIP2, KIT, MET, AKT1, ALK, BARD1, BRAF, CD274, ERBB2, FGFR1, IDH2, NOTCH1, RET, and STK11 (in descending order of occurrence). TP53 mutations were identified in the TNBC group more frequently than in the HR+/HER2 group (p=0.003). The presence of TP53 mutations was associated with a higher tumor grade (p=0.008), p53 positivity (p<0.0001), and a higher (≥15) Ki-67 index (p=0.004). PIK3CA was the most frequently mutated gene in HR+/HER2 breast cancer (8/22, 36.4%), but not in TNBC (1/12, 8.3%). However, circulating cell-free PIK3CA mutations were not detected in either group. ConclusionsThe TP53 mutation is associated with higher tumor grade and Ki-67 expression in both groups, and with larger tumor size in TNBC, but not in HR+/HER2– breast cancer. In the foundation of TP53 mutation, concomitant mutation numbers are proportional to tumor size, reflecting clonal progression. Breast cancer-associated mutations such as those in TP53 and PIK3CA have different biological implications for the proliferation and clonal diversification of these two distinct groups of breast cancer.

scholarly journals Current Landscape of Targeted Therapy in Hormone Receptor-Positive and HER2-Negative Breast Cancer

2021 ◽  
Vol 28 (3) ◽  
pp. 1803-1822
Author(s):  
Samitha Andrahennadi ◽  
Amer Sami ◽  
Mita Manna ◽  
Mehrnoosh Pauls ◽  
Shahid Ahmed
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
High Risk ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Early Stage ◽  
Treatment Options ◽  
Mtor Inhibitors ◽  
Hormone Receptor Positive

Background: Hormone receptor-positive and HER2-negative breast cancer (HR + BC) is the most prevalent breast cancer. Endocrine therapy is the mainstay of treatment, however, due to the heterogeneous nature of the disease, resistance to endocrine therapy is not uncommon. Over the past decades, the emergence of novel targeted therapy in combination with endocrine therapy has shown improvement in outcomes of HR + BC. This paper reviews available data of targeted therapy and the results of pivotal clinical trials in the management of HR + BC. Methods: A literature search in PubMed and Google Scholar was performed using keywords related to HR + BC and targeted therapy. Major relevant studies that were presented in international cancer research conferences were also included. Results: Endocrine therapy with tamoxifen and aromatase inhibitors are backbone treatments for women with early-stage HR + BC leading to a significant reduction in mortality. They can also be used for primary prevention in women with a high risk of breast cancer. Preliminary data has shown the efficacy of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, in high-risk disease in combination with aromatase inhibitors. For most women with advanced HR + BC, endocrine therapy is the primary treatment. Recent evidence has shown that the use of CKD 4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors in combination with endocrine therapy has been associated with better outcomes and delays initiation of chemotherapy. Several novel agents are under study for HR + BC. Discussion: Targeted treatment options for HR + BC have evolved. The future of overcoming resistance to targeted therapy, novel compounds, and predictive markers are key to improving HR + BC outcomes.

scholarly journals Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2− Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-11
Author(s):  
Kai Hong ◽  
Lingli Yao ◽  
Xianneng Sheng ◽  
Dan Ye ◽  
Yu Guo
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Library ◽  
Cyclin Dependent Kinase ◽  
Residual Cancer Burden ◽  
Her2 Breast Cancer

<b><i>Background:</i></b> Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. <b><i>Objective:</i></b> The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2− BC. <b><i>Method:</i></b> We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. <b><i>Results:</i></b> Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 &#x3c; 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81–13.03, <i>p</i> &#x3c; 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39–34.58, <i>p</i> = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17–35.88, <i>p</i> &#x3c; 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04–2.85, <i>p</i> = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59–29.61, <i>p</i> &#x3c; 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40, <i>p</i> = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41–20.11, <i>p</i> &#x3c; 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29–0.87, <i>p</i> = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12–2.07, <i>p</i> = 0.342) and reduce the residual cancer burden (RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, <i>p</i> = 0.121; RCB 2–3: OR = 2.30, 95% CI = 0.89–5.91, <i>p</i> = 0.084). <b><i>Conclusions:</i></b> The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.

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